Contact information
Research groups
David Cruz Hernandez
B.A Chemistry. B.S Molecular and Cellular Biology. M.S Stem Cell Biology. DPhil in Medical Sciences
Postdoctoral Scientist
Research Intereset
Acute leukaemia, like most blood cancers, arises from the accumulation of multiple genetic or epigenetic changes in normal cells. These changes are gradually acquired and progressively induce cellular differentiation arrest. Therefore, leukaemias are preceded by a preleukemic state where some but not all genetic or epigenetic changes provide a clonal advantage and delay cellular differentiation. A comprehensively understanding of this preleukemic state can offer opportunities for early diagnosis, prevention and eradication of leukaemia propagating cells.
For instance, myeloid leukaemia of Down syndrome (ML-DS), an acute leukaemia with megakaryoblastic and erythroid features, is preceded by a temporally distinct but clonally related preleukemic state known as Transient abnormal myelopoiesis or TAM. TAM arises from the cooperation of trisomy 21 and a truncating mutation in the gene encoding the key transcription factor GATA1. Single allele mutations in genes encoding the cohesin complex are often required to transform the preleukemic clone into frank leukaemia. Despite having a comprehensive understanding of the genetic lesion required for leukaemia transformation, a complete molecular mechanism of differentiation arrest is not yet known.
As a DPhil student in the Vyas lab, I employ gene editing technologies, transcription factor occupancy mapping technologies, multiparameter flow cytometry, as well as state of the art single cell transcriptomics, with the goal of understanding the molecular mechanism of differentiation delay/arrest caused by oncogenic cooperation between mutant GATA1 and trisomy 21.
Colleges
Recent publications
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RUNX1 loss renders hematopoietic and leukemic cells dependent on interleukin-3 and sensitive to JAK inhibition
Journal article
Fan AC. et al, (2023), Journal of Clinical Investigation
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Data from The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and <i>TET2</i>-Mutant Preleukemia
Other
Nakauchi Y. et al, (2023)
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Data from The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and <i>TET2</i>-Mutant Preleukemia
Other
Nakauchi Y. et al, (2023)
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Supplementary Figure from The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and <i>TET2</i>-Mutant Preleukemia
Other
Nakauchi Y. et al, (2023)
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Supplementary Figure from The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and <i>TET2</i>-Mutant Preleukemia
Other
Nakauchi Y. et al, (2023)
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Supplementary Table from The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and <i>TET2</i>-Mutant Preleukemia
Other
Nakauchi Y. et al, (2023)
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Supplementary Table from The Cell Type–Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and <i>TET2</i>-Mutant Preleukemia
Other
Nakauchi Y. et al, (2023)
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The cell type specific 5hmC landscape and dynamics of healthy human hematopoiesis and TET2-mutant pre-leukemia
Journal article
Nakauchi Y. et al, (2022), Blood Cancer Discovery
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IL-3 SELECTIVELY RESCUES RUNX1-DEFICIENT HUMAN HSPCS WITH DYSREGULATED JAK/STAT SIGNALING
Conference paper
Fan A. et al, (2022), EXPERIMENTAL HEMATOLOGY, 111, S84 - S84
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Oncogenic Gata1 causes stage-specific megakaryocyte differentiation delay.
Journal article
Juban G. et al, (2021), Haematologica, 106, 1106 - 1119
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HYPERSENSITIVITY TO IL-3 RESCUES INFLAMMATORY RUNX1-DEFICIENT HUMAN HSPCS
Conference paper
Fan A. et al, (2021), EXPERIMENTAL HEMATOLOGY, 100, S48 - S48
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Sensitive, rapid diagnostic test for transient abnormal myelopoiesis and myeloid leukemia of Down syndrome.
Journal article
Cruz Hernandez D. et al, (2020), Blood, 136, 1460 - 1465
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Myeloid Pre-Leukemia and Leukemia of Down Syndrome
Journal article
Cruz Hernandez D. and VYAS P., (2020), HemaSphere
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GATA1 and cooperating mutations in myeloid leukaemia of Down syndrome.
Journal article
Garnett C. et al, (2020), IUBMB Life, 72, 119 - 130
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Oncogenic Drivers and Development.
Journal article
Cruz Hernandez D. and Vyas P., (2019), Cancer Discov, 9, 1653 - 1655
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Mechanisms of Progression of Myeloid Preleukemia to Transformed Myeloid Leukemia in Children with Down Syndrome.
Journal article
Labuhn M. et al, (2019), Cancer Cell, 36
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Mechanisms of Progression of Myeloid Preleukemia to Transformed Myeloid Leukemia in Children with Down Syndrome.
Journal article
Labuhn M. et al, (2019), Cancer Cell, 36, 123 - 138.e10
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MODELING THE PATHOGENESIS OF RUNX1 DEFICIENCY IN INHERITED AML PREDISPOSITION SYNDROMES IN PRIMARY CELLS
Conference paper
Fan A. et al, (2019), EXPERIMENTAL HEMATOLOGY, 76, S65 - S65
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Correction: Multiplexed genetic engineering of human hematopoietic stem and progenitor cells using CRISPR/Cas9 and AAV6.
Journal article
Bak RO. et al, (2018), Elife, 7
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Generation and use of a humanized bone-marrow-ossicle niche for hematopoietic xenotransplantation into mice
Journal article
Reinisch A. et al, (2017), Nature Protocols, 12, 2169 - 2188
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Multiplexed genetic engineering of human hematopoietic stem and progenitor cells using CRISPR/Cas9 and AAV6.
Journal article
Bak RO. et al, (2017), Elife, 6
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Multiplexed genetic engineering of human hematopoietic stem and progenitor cells using CRISPR/Cas9 and AAV6
Journal article
Bak RO. et al, (2017), ELIFE, 6
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Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data
Journal article
Sinha S. et al, (2017), Nature Communications, 8