Publications by authors named "Mellissa Alcantara"

The major concern with COVID-19 therapeutic monoclonal antibodies is the loss of efficacy against continuously emerging variants of SARS-CoV-2. To predict antibody efficacy against future Omicron subvariants, we conducted deep mutational scanning (DMS) encompassing all single mutations of the receptor-binding domain of the BA.2 strain utilizing an inverted infection assay with an ACE2-harboring virus and library spike-expressing cells.

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While androgen is considered a pivotal regulator of sexually dimorphic development, it remains unclear how it orchestrates the differentiation of reproductive organs. Using external genitalia development as a model, we showed that androgen, through the transcription factor , induced cell migration by remodeling the local extracellular matrix (ECM), leading to increased cell contractility and focal adhesion assembly. Furthermore, we identified the matrix metalloproteinase as a target gene under androgen signaling.

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Article Synopsis
  • Industrial chemicals, particularly those identified as antiandrogens, pose risks to human health by affecting the development of reproductive organs, specifically embryonic external genitalia (eExG).
  • The study demonstrates the effectiveness of the eExG slice culture assay in evaluating the impacts of endocrine-disrupting chemicals—focusing on diazinon, dibutyl phthalate, and fenitrothion (FNT)—on urethra formation.
  • Results indicate that FNT disrupts androgen signaling by decreasing androgen receptor expression, leading to defects in androgen-induced urethral masculinization, while diazinon and dibutyl phthalate did not show similar effects.
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External genitalia development in mice involves multiple developmental processes under the regulation of various signaling pathways. Wnt5a, one of the major Wnt ligands, is a crucial developmental regulator of outgrowing organs such as the limb, the mandible, and the external genitalia. Defects in Wnt5a signaling have been linked to Robinow syndrome, a genetic disorder in which male patients manifest a micropenis and defective urethral tube formation.

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Article Synopsis
  • * The Hh ligands, which are usually released from epithelial cells, influence nearby mesenchymal cells through paracrine signaling, presenting a way to study the relationship of epithelial-mesenchymal interactions (EMI) with other pathways like hormonal signaling.
  • * The review will focus on (1) the interaction between Hh and androgen signaling, and (2) how communication between epithelial and mesenchymal cells affects the basement membrane and extracellular matrix in both organ development and the context of prostate cancer.
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The morphogenesis of mammalian embryonic external genitalia (eExG) shows dynamic differences between males and females. In genotypic males, eExG are masculinized in response to androgen signaling. Disruption of this process can give rise to multiple male reproductive organ defects.

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Development of external genitalia and perineum is the subject of developmental biology as well as toxicology and teratology researches. Cloaca forms in the lower (caudal) end of endoderm. Such endodermal epithelia and surrounding mesenchyme interact with various signals to form the external genitalia.

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