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Mensah, C.

Publications and source records attributed to Mensah, C..

2 recordsLinked to original sources

Characterising recent antimalarial resistance in West Africa: Insights from amplicon sequencing of 17,384 Plasmodium falciparum infection samples

Plasmodium falciparum (P. falciparum) infection remains a significant public health threat in West Africa, where chemoprevention and first-line therapies are key interventions against malaria. However, the development and spread of resistance to commonly used antimalarials poses a growing threat to the efficacy of these strategies. This study characterises the recent landscape of antimalarial resistance in West Africa by analysing targeted amplicon sequences from 17,384 P. falciparum infection samples. Across countries, the prevalence of the pyrimethamine resistance-associated dhfr triple mutant allele (51I/59R/108N) exceeded 80%, while its combination with the sulphadoxine resistance-associated dhps 437G exceeded 60% of infections. Unlike the parasite genotypes in East Africa, the prevalence of the dhps 540E mutant was low (1.5%), whereas dhps 436A was common (43.8%). The chloroquine resistance marker crt 76T showed greatest geographic heterogeneity, ranging from low prevalence in Ghana (1.3%) to very common in The Gambia (64.9%). Non-synonymous mutants of kelch13 were uncommon, most with unknown relevance to artemisinin resistance and observed for the first time in Africa. However, mutants that are artemisinin resistance-associated elsewhere were detected in three infection samples from Ghana (574L, 561H, 469Y), and one in Cameroon (538V). This large-scale genomic surveillance of P. falciparum infections highlights the need for ongoing monitoring of drug resistance and for data integration throughout the region.

genomics↗

Adaptive Responses Directed by CREB Control Epithelial-Mesenchymal Plasticity in Cancer

Cellular plasticity plays essential roles in development including organogenesis and tissue homeostasis. The epithelial-to-mesenchymal transition (EMT) is no longer considered a binary switch but rather a dynamic process characterized by a continuum of metastable intermediates having unique features. This epithelial-mesenchymal (E/M) plasticity can be co-opted by cancer cells to promote dedifferentiation that results in hybrid E/M states which increase tumor heterogeneity and generate distinct molecular and phenotypic adaptations that promote drug resistance, dormancy, recurrence, and/or cell invasion and metastasis. The mechanisms that coordinate and maintain metastable hybrid E/M states are poorly understood, and here we report they are controlled by the master transcription factor CREB which regulates adaptive response genes necessary for E/M plasticity. Specifically, a CREB-dependent head and neck cancer model validated the role of CREB in cancer cell plasticity and revealed that it controls a non-canonical EMT gene signature. Moreover, analyses of this signature across cancer types identified the transcriptional regulators VGLL3 and KLF3 as core PanCancer mediators of hybrid E/M states, and gain- and loss-of-function studies established that CREB regulates E/M plasticity by coordinating VGLL3 and KLF3 to drive metastasis.

cell biology↗