Biology subjects

Sater, H.

Publications and source records attributed to Sater, H..

2 recordsLinked to original sources

bioRxiv2022

Epigenetic silencing by SMYD3 represses tumor intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck.

Cancers often display immune escape, but the mechanisms and potential for reversibility are incompletely understood. Epigenetic dysregulation has been implicated in the immune escape of various cancer types. We have identified the epigenetic modifier SET and MYND-domain containing protein 3 (SMYD3) as a mediator of immune escape in human papilloma virus (HPV)- negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor prognosis and low response to immunotherapy with pembrolizumab, a programmed-death-1 (PD-1) targeting antibody. SMYD3 loss increased the sensitivity of HNSCC cancer cells to IFN-{beta}, resulting in upregulation of type I IFN response and antigen presentation machinery genes. We found that SMYD3 regulates the transcription of Ubiquitin-Like PHD And RING Finger Domain- Containing Protein 1 (UHRF1), a key epigenetic reader of trimethylated lysine 9 on histone H3 (H3K9me3), which binds to H3K9me3-enriched promoters of key immune-related genes and silences their expression. SMYD3 further maintains the repression of immune-related genes through the deposition of H4K20me3 within the gene body regions of these genes. In an anti-PD-1 immune checkpoint resistant syngeneic mouse model of HPV-negative HNSCC, Smyd3 depletion induced influx of CD8+ T-cells, upregulated PD-L1 and MHC class I molecules, and increased sensitivity to anti-PD-1 therapy. SMYD3 overexpression was associated with decreased CD8 T-cell infiltration in tumor samples from patients with HPV-negative HNSCC, and was associated with poor response to pembrolizumab. Overall, these data highlight a previously unreported function of SMYD3 as a master epigenetic regulator of anti-tumor immune response in HPV-negative HNSCC and provide a rationale for translational approaches combining SMYD3 depletion strategies with checkpoint blockade to overcome anti-PD-1 resistance in this devastating disease.

cancer biology↗

bioRxiv2021

Terpene volatiles mediates the chemical basis of blueberry aroma and consumer acceptability

Among the main features treasured by blueberry consumers, flavor is the most important. Human perception of food flavors can primarily be divided into two main sensory inputs, taste and aroma. Through retronasal olfaction, a group of metabolites called volatile organic compounds (VOCs) emitted from the fruit are able to produce the sensation of aroma, creating the myriad of flavors experienced during our life. In blueberry, breeders have noticed some genotypes with unique floral and sweet flavor notes that, ultimately, enhance human aroma perception. Despite the importance, both the understanding of which chemicals are mediating this variation across phenotypes and the potential impact on consumer preferences remains largely unknown. In this study we dissected the main components underlying blueberry aroma and associated it with consumer predilections by paring metabolomics with sensory analysis. Our contribution in this study is four-fold: (i) first, based on a representative blueberry germplasm cultivated at the University of Florida, we differentiated genotypes with floral and sweet aromatic notes and confirmed that such unique characteristics are preferred by consumers; (ii) at the chemical level, we showed that a group of eight terpene volatiles constitute the primary metabolic group associated with aroma sensation; (iii) we demonstrated that aromatic genotypes can be classified using information from a group of a few key volatiles; and finally, (iv) we combined pedigree and metabolomic information in a single predictive framework and showed the importance of metabolomic data for flavor-assisted selection. For the blueberry community, our findings open new venues to explore flavor. Broadly, we present an emerging view about flavor and provide a detailed blueprint of how this target could be addressed in fruits and vegetables.

genetics↗