Project description:Blastocladiomycota, early diverging zoosporic (flagellated) lineages of fungi, are vastly understudied. This phylum includes the genus Coelomomyces which consists of more than eighty fungal species that are obligate parasites of arthropods. Coelomomyces lack a complete asexual life cycle, instead surviving through an obligate heteroecious alternation of generations life cycle. Despite their global distribution and interesting life cycle, little is known about Coelomomyces species. To begin to address this, we analyzed transcriptomes from across host-associated life stages including infection of larva and excised mature sporangia from the mosquito, Anopheles quadrimaculatus. We identified differentially expressed genes and over-enriched GO terms both across and within life stages and used these to make hypotheses about C. lativittatus biology. Generally, we found the C. lativittatus transcriptome to be a complex and dynamic expression landscape; GO terms related to metabolism and transport processes were over-enriched during infection and terms related to dispersal were over-enriched during sporulation. The C. lativittatus transcriptomes reported here are a valuable resource and may be leveraged toward furthering understanding of the biology of these and other early diverging fungal lineages.

2023-01-21 | GSE222209 | GEO

AVA-ADR-001- a small molecular inhibitor of ADAR1 (Immuno-oncology target)

Project description:To inhibitors for ADAR1 and a strong rationale for the development of ADAR1 p150 inhibitors for cancer immunotherapy Here, we describe AVA-ADR-001, a potential first-in-class small molecule inhibitor of ADAR1 p150 targeting the Z alpha domain. AVA-ADR-001 binds specifically to the Z alpha domain of ADAR1 p150 as confirmed by fluorescence spectroscopy and showed significant interferon induction in THP1 macrophages, which have high ADAR1 p150 expression compared with monocytes. Proteomics and transcriptomics analysis revealed significant upregulation of interferon signaling upon treatment with AVA-ADR -001. Interestingly, activation of interferon signaling resulted in AVA-ADR-001 induced cell killing in ADAR1-independent cell lines. In addition, treatment with AVA-ADR -001 resulted in significant activation of PKR, which may explain the decreased cell proliferation. Finally, AVA-ADR-001 showed superior anti-tumor efficacy compared to anti-PD1 in an in vivo tumor efficacy study and has a moderately synergistic effect when combined. Overall, this study reveals that ADAR1 p150 inhibition by AVA-ADR-001 exerts a multipronged impact on anti-tumor efficacy mediated by immune cells, accumulation of interferons and activation of PKR, resulting in protein translation inhibition and cell proliferation arrest.

2023-04-17 | GSE229503 | GEO

Genomic resources enable study of the blastoclad fungus, Coelomomyces lativittatus, an obligate parasite of mosquitoes and microcrustaceans, during infection and sporulation

Project description:Genomic resources enable study of the blastoclad fungus, Coelomomyces lativittatus, an obligate parasite of mosquitoes and microcrustaceans, during infection and sporulation

| PRJNA918605 | ENA

Overcoming resistance to anti-VEGF therapy via epigenetic regulation of BARD1 [OVCAR8ip1 BARD1 overexpression]

Project description:Despite widespread use of anti-vascular endothelial growth factor (VEGF) antibody (AVA) for cancer therapy, most patients develop progressive disease after initial response. Therefore, novel strategies are needed to understand and overcome AVA resistance. Here, we identify an unexpected role of BRCA1-associated RING domain 1 (BARD1) in overcoming adaptive resistance to AVA. We investigated the effects of epigenetic modulation on cellular response to AVA; in particular, the molecular effects of both global and targeted DNA methylation. Using in vitro assays, BARD1 was identified as being specifically involved in angiogenesis. Sequential treatment with azacytidine overcame AVA therapy resistance in cancer models in vivo. We further demonstrated that specifically targeting BARD1 with either small-interfering RNA or CpG-targeted demethylation reduced tumor growth when combined with AVA therapy (compared with AVA alone) in mouse models of ovarian cancer. These results identify a previously unrecognized role for BARD1 in tumor angiogenesis and show that targeted restoration of BARD1 can enhance the efficacy of AVA therapy in cancer models.

2025-06-16 | GSE247653 | GEO

Overcoming resistance to anti-VEGF therapy via epigenetic regulation of BARD1 [SKOV3 BARD1 siRNA-RNASeq]

2025-06-17 | GSE247654 | GEO