Project description:Acute myeloid leukemia (AML) and DNMT3A mutations (DNMT3Amut) are considered to carry intermediate risk under the 2022 European LeukemiaNet (ELN-2022) classification in the absence of other co-mutations or cytogenetic abnormalities. However, this group is highly heterogeneous. In this study, the genomic and transcriptomic features influencing outcomes in DNMT3A-mutated AML were examined in a cohort of 884 patients with AML receiving standard chemotherapy. Stratification by NPM1 and FLT3-ITD status revealed worse survival among patients with NPM1 mutations and wild-type FLT3-ITD (NPM1mut/FLT3-ITDwt) than patients in the ELN-2022 favorable risk group. The other three subgroups (NPM1mut/FLT3-ITDmut, NPM1wt/FLT3-ITDmut, and NPM1wt/FLT3-ITDwt) exhibited worse prognoses than patients in the ELN-2022 intermediate risk group. Additionally, the presence of TET2mut in patients with AML and DNMT3Amut/NPM1mut/FLT3-ITDwt led to reclassification from favorable risk to intermediate risk in the ELN-2022. RNA-sequencing analysis revealed a distinct transcriptomic profile in patients with TET2mut, highlighting the enrichment of leukemic stem cell signatures and dendritic cell migration, with MMP14, CD200, and CT45A5 identified as key differentially expressed genes. In conclusion, co-mutation patterns strongly affected AML outcomes in patients with DNMT3Amut. Patients with TET2mut constituted a unique subgroup within the ELN-2022 favorable DNMT3Amut/NPM1mut/FLT3-ITDwt group, characterized by distinct transcriptomic features and an unfavorable prognosis.
Project description:The present study investigated whether maternal periodontal disease modifies the microRNA expression profile in adult offspring. *************************************************************** This study was supported by the São Paulo Research Foundation (FAPESP) [grant #2019/04183-9; #2022/08872-6; #2023/03786-7; #2023/12488-0; #2023/01400-4] and CNPq [grant 151151/2023-7], São Paulo, SP, Brazil. The grants #2019/04183-9; #2023/12488-0; #2023/01400-4 and 151151/2023-7 were awarded to the author Maria Sara de Lima Coutinho Mattera. The grant #2022/08872-6 was awarded to Heloisa Macedo Sampaio. The grant #2023/03786-7 was awarded to Gabriele Fernandes Baliero. ***************************************************************
Project description:The outbreak-causing monkeypox virus of 2022 (2022 MPXV) is classified as a clade IIb strain and phylogenetically distinct from prior endemic MPXV strains (clades I or IIa), suggesting that its virological properties may also differ. Here, we used human keratinocytes and induced pluripotent stem cell-derived colon organoids to examine the efficiency of viral growth in these cells and the MPXV infection-mediated host responses. MPXV replication was much more productive in keratinocytes than in colon organoids. We observed that MPXV infections, regardless of strain, caused cellular dysfunction and mitochondrial damage in keratinocytes. Notably, a significant increase in the expression of hypoxia-related genes was observed specifically in 2022 MPXV-infected keratinocytes. Our comparison of virological features between 2022 MPXV and prior endemic MPXV strains revealed signaling pathways potentially involved with the cellular damages caused by MPXV infections and highlights host vulnerabilities that could be utilized as protective therapeutic strategies against human mpox in the future.
Project description:VSMCs expressing SCA1 have increased proliferative capacity (Dobnikar et al, 2018; Worssam et al, 2022; Pan et al, 2020). We therefore, mapped chromatin accessibility changes using bulk ATAC-seq for SCA1+ and SCA1- lineage traced VSMCs.
Project description:As training dataset for Random Promoter DREAM Challenge 2022, we generated ~6.7 million synthetic promoters (in yeast) comprised of random DNA (N80) and measured their expression by FACS (sorting into 18 bins). As test dataset for Random Promoter DREAM Challenge 2022, we generated ~71k synthetic promoters (in yeast) comprised of designed DNA (NBT) and measured their expression by FACS (sorting into 18 bins).