Dorien Pastoors
@dpastoors.bsky.social
Postdoc at DFCI, Boston, USA | molecular biology & hematology 🧫 | data visualization in #ggplot | swimming, running, baking | HemeSky feed
Excited to share that I started as a Postdoctoral Fellow in @tothovalab.bsky.social at @danafarber.bsky.social in Boston! Looking forward to the next years of molecular & myeloid biology in Boston 🤩🌇
September 20, 2025 at 2:05 AM
Excited to share that I started as a Postdoctoral Fellow in @tothovalab.bsky.social at @danafarber.bsky.social in Boston! Looking forward to the next years of molecular & myeloid biology in Boston 🤩🌇
Yesterday I successfully defended my PhD thesis!!! It was a fantastic day where I got to celebrate with many colleagues, friends and family (this smile was on my face all day long)
June 27, 2025 at 5:56 PM
Yesterday I successfully defended my PhD thesis!!! It was a fantastic day where I got to celebrate with many colleagues, friends and family (this smile was on my face all day long)
Thanks for the opportunity to present our work at the last day of #EHA2025 🤩 on MECOM as a repressor of CEBPA - also see our recent preprint: www.biorxiv.org/content/10.1... and I very much hope you can stay tuned for the final version soon-ish) #erasmusmcblood #hemesky
June 15, 2025 at 8:34 PM
Thanks for the opportunity to present our work at the last day of #EHA2025 🤩 on MECOM as a repressor of CEBPA - also see our recent preprint: www.biorxiv.org/content/10.1... and I very much hope you can stay tuned for the final version soon-ish) #erasmusmcblood #hemesky
Spotted fellow #erasmusmcblood PhD candidate @shordijk.bsky.social at the #EHA wall of fame for her Mobility grant 🤩🤩 Congratulations !! @clotterdam.bsky.social
June 12, 2025 at 10:49 AM
Spotted fellow #erasmusmcblood PhD candidate @shordijk.bsky.social at the #EHA wall of fame for her Mobility grant 🤩🤩 Congratulations !! @clotterdam.bsky.social
SUPER excited to share that I got my PhD thesis - thanks to a special delivery from @massaarsanne.bsky.social to Milan!! On the 26th of June, I will defend my thesis at 15:30 CET. You can follow online at eur.cloud.panopto.eu/Panopto/Page... #hemesky
June 8, 2025 at 1:08 PM
SUPER excited to share that I got my PhD thesis - thanks to a special delivery from @massaarsanne.bsky.social to Milan!! On the 26th of June, I will defend my thesis at 15:30 CET. You can follow online at eur.cloud.panopto.eu/Panopto/Page... #hemesky
This Thursday, I will be part of the @oncodeinstitute.bsky.social team to cycle up the Alpe d'Huez - a (very steep!!!!) mountain in the French Alps - to raise money for the Dutch Cancer Society @liting-chen.bsky.social
June 3, 2025 at 4:32 PM
This Thursday, I will be part of the @oncodeinstitute.bsky.social team to cycle up the Alpe d'Huez - a (very steep!!!!) mountain in the French Alps - to raise money for the Dutch Cancer Society @liting-chen.bsky.social
Wooo - check the cover image of the current issue of Blood Advances by @massaarsanne.bsky.social & Emma Boertjes et al!!! Congratulations - methylation damage repair is impaired by double mutations in DNMT3A in AML
March 21, 2025 at 7:26 AM
Wooo - check the cover image of the current issue of Blood Advances by @massaarsanne.bsky.social & Emma Boertjes et al!!! Congratulations - methylation damage repair is impaired by double mutations in DNMT3A in AML
Haha yes indeed !! I leave mine for longer - this is my version
January 9, 2025 at 4:20 PM
Haha yes indeed !! I leave mine for longer - this is my version
Overexpression of 4xPLDLS significantly upregulates CEBPA and induces partial differentiation. The effect size is not as big as when MECOM is depleted, suggesting that there are more mechanisms in play causing CEBPA repression by MECOM. [13/15]
January 6, 2025 at 3:46 PM
Overexpression of 4xPLDLS significantly upregulates CEBPA and induces partial differentiation. The effect size is not as big as when MECOM is depleted, suggesting that there are more mechanisms in play causing CEBPA repression by MECOM. [13/15]
Taken together, this supports a repressive role of MECOM on CEBPA transcription. Can this be targeted? CTBP2 is a co-repressor required for MECOM driven leukemogenesis (www.science.org/doi/10.1126/... ): We developed a 4 X PLDLS construct that blocks CTBP binding to MECOM [12/15]
January 6, 2025 at 3:46 PM
Taken together, this supports a repressive role of MECOM on CEBPA transcription. Can this be targeted? CTBP2 is a co-repressor required for MECOM driven leukemogenesis (www.science.org/doi/10.1126/... ): We developed a 4 X PLDLS construct that blocks CTBP binding to MECOM [12/15]
As part of this paper, we are also releasing a set of new RNA-seq data of a large cohort of patients with 3q26 rearrangements collected over the years, including the classical inv(3)/t(3;3) as well as t(3;x). These patients show reduced expression of CEBPA. [11/15]
January 6, 2025 at 3:46 PM
As part of this paper, we are also releasing a set of new RNA-seq data of a large cohort of patients with 3q26 rearrangements collected over the years, including the classical inv(3)/t(3;3) as well as t(3;x). These patients show reduced expression of CEBPA. [11/15]
Direct overexpression of CEBPA cDNA in presence of MECOM in 3q26r-MUTZ3 cells bypasses the MECOM-induced block of myeloid differentiation.[10/15]
January 6, 2025 at 3:46 PM
Direct overexpression of CEBPA cDNA in presence of MECOM in 3q26r-MUTZ3 cells bypasses the MECOM-induced block of myeloid differentiation.[10/15]
We derived clones with heterozygous deletion of the +42kb CEBPA enhancer and these do not differentiate upon MECOM loss, indicating the +42kb enhancer is required to release the repression imposed by MECOM on CEBPA. [9/15]
January 6, 2025 at 3:46 PM
We derived clones with heterozygous deletion of the +42kb CEBPA enhancer and these do not differentiate upon MECOM loss, indicating the +42kb enhancer is required to release the repression imposed by MECOM on CEBPA. [9/15]
CEBPA is a TF that is critical for myeloid development. A set of its target genes are upregulated upon MECOM shRNA k.d.. CEBPA motifs are predicted to gain binding of their TF. In addition, CEBP motifs are enriched in upregulated H3K27ac, RUNX1 and P300 peaks compared to unchanged peaks. [8/15]
January 6, 2025 at 3:46 PM
CEBPA is a TF that is critical for myeloid development. A set of its target genes are upregulated upon MECOM shRNA k.d.. CEBPA motifs are predicted to gain binding of their TF. In addition, CEBP motifs are enriched in upregulated H3K27ac, RUNX1 and P300 peaks compared to unchanged peaks. [8/15]
Using ATAC-seq we found the most significant differentially accessible region upon MECOM loss is a previously described +42kb enhancer of CEBPA. MECOM indeed binds to this region, together with its co-repressor CTBP2. Depletion of MECOM increases H3K27ac at this enhancer. [6/15]
January 6, 2025 at 3:46 PM
Using ATAC-seq we found the most significant differentially accessible region upon MECOM loss is a previously described +42kb enhancer of CEBPA. MECOM indeed binds to this region, together with its co-repressor CTBP2. Depletion of MECOM increases H3K27ac at this enhancer. [6/15]
Our model also enabled investigating immediate changes in gene expression applying SLAM-seq (3hrs). We mostly found upregulated genes upon MECOM depletion. CEBPA was also upregulated when MECOM is eliminated by shRNA k.d. or CRISPR-Cas9 mutations in the translocated GATA2 enhancer. [5/15]
January 6, 2025 at 3:46 PM
Our model also enabled investigating immediate changes in gene expression applying SLAM-seq (3hrs). We mostly found upregulated genes upon MECOM depletion. CEBPA was also upregulated when MECOM is eliminated by shRNA k.d. or CRISPR-Cas9 mutations in the translocated GATA2 enhancer. [5/15]
MECOM depletion induces myeloid differentiation over time. Interestingly, during the differentiation, GFP (which is not degraded by auxin) goes down – which indicates differentiation switches off the ectopic GATA2 enhancer which activates MECOM in those leukemia cells. [4/15]
January 6, 2025 at 3:46 PM
MECOM depletion induces myeloid differentiation over time. Interestingly, during the differentiation, GFP (which is not degraded by auxin) goes down – which indicates differentiation switches off the ectopic GATA2 enhancer which activates MECOM in those leukemia cells. [4/15]
For this reason, disruption of MECOM leads to a rapid onset of differentiation that makes it difficult to separate direct from indirect effects. We addressed this challenge using an endogenous MECOM degron model (MECOM-AID-T2A-eGFP) where we can rapidly (1.5 hrs) deplete MECOM with auxin. [3/15]
January 6, 2025 at 3:46 PM
For this reason, disruption of MECOM leads to a rapid onset of differentiation that makes it difficult to separate direct from indirect effects. We addressed this challenge using an endogenous MECOM degron model (MECOM-AID-T2A-eGFP) where we can rapidly (1.5 hrs) deplete MECOM with auxin. [3/15]
Can we discuss these Daily Paper water marked jeans/jackets and how they show nucleosomes! A puzzling case for the @nucleosomepolice.bsky.social ?!
December 3, 2024 at 7:39 PM
Can we discuss these Daily Paper water marked jeans/jackets and how they show nucleosomes! A puzzling case for the @nucleosomepolice.bsky.social ?!
Great molecular aspects of hematology meeting organised pre-EHA by our department, with many fantastic (keynote) speakers in rainy Rotterdam. I got to present, as well as other PhDs from NL and abroad - including @jstauber.bsky.social - #bloodsky
June 13, 2024 at 9:11 AM
Great molecular aspects of hematology meeting organised pre-EHA by our department, with many fantastic (keynote) speakers in rainy Rotterdam. I got to present, as well as other PhDs from NL and abroad - including @jstauber.bsky.social - #bloodsky
This is in line with a cell line-xenograft model of MUTZ3 transplanted onto scaffolds in mice, which could only grow out with PLASS, but not PLDLS.
May 16, 2024 at 1:29 PM
This is in line with a cell line-xenograft model of MUTZ3 transplanted onto scaffolds in mice, which could only grow out with PLASS, but not PLDLS.
In human AML line SB1690CB and MUTZ3 cells, PLDLS-inhibitor transduced cells were always outcompeted by PLASS (Control) transduced cells in vitro...
May 16, 2024 at 1:29 PM
In human AML line SB1690CB and MUTZ3 cells, PLDLS-inhibitor transduced cells were always outcompeted by PLASS (Control) transduced cells in vitro...
In mBM, EVI1-immortalised cells were no longer able to form colonies in presence of PLDLS inhibitor (in contrast to normal mBM or E2A-PBX transformed mBM) and this reinstated neutrophilic differentiation.
May 16, 2024 at 1:29 PM
In mBM, EVI1-immortalised cells were no longer able to form colonies in presence of PLDLS inhibitor (in contrast to normal mBM or E2A-PBX transformed mBM) and this reinstated neutrophilic differentiation.