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Biology subjects

Chugh, D.

Publications and source records attributed to Chugh, D..

2 recordsLinked to original sources

Spatial transcriptomic analysis of progressing oral epithelial dysplasia reveals unique differentially expressed genes and microenvironmental changes.

Oral squamous cell carcinoma (OSCC) often arises from oral epithelial dysplasia (OED); however, the gene expression changes during OED progression and its microenvironment are not fully understood. This study used spatial transcriptomics to identify differentially expressed genes and microenvironmental alterations associated with OEDs malignant transformation of OED. A ten-year retrospective analysis of paired OSCC and prior OED samples was conducted at the University of Toronto Oral Pathology Laboratory. A total of 24 paired progressing OED cases and 23 matched non-progressing OED cases were examined using spatial transcriptomics in PanCK+ (dysplastic epithelium or OSCC) and PanCK- (stroma) regions. The analysis included differential gene expression, pathway analysis and spatial deconvolution. Three genes (STOM, KIF26A, and CDKN2A) showed increased expression in the epithelial component of progressing OED compared with non-progressing OED, whereas 41 genes were differentially expressed in OSCC versus the precursor samples. Ubiquitination-related pathways were enriched during OED progression. Functional validation identified TNFRSF12A (Fn14) as a potential regulator of OED progression to OSCC. The OSCC microenvironment displayed increased numbers of fibroblasts, neutrophils, monocytes, and mast cells compared with that of the precursor samples. Our findings suggest that spatial profiling of OED can help identify unique gene signatures and microenvironmental changes that occur before the malignant transformation.

cancer biology↗

Polyimide-Based Flexible Multi-Electrode Arrays: Synthesis, Microfabrication, and in-vivo Validation

Neurological disorders such as epilepsy, Parkinsons disease, are rising globally, with conditions like drug-resistant epilepsy affecting millions of patients for whom traditional pharmacological treatments are ineffective. Implantable neural devices have shown great promise in managing these conditions, but their accessibility is limited due to high costs and the availability of suitable biocompatible materials.Thin film implantable neural interfaces hold immense promise over conventional clinical electrodes, offering higher resolution, flexibility, and improved integration with neural tissue. However, their widespread use, especially for flexible interfaces, is limited by the lack of customizable and medical grade materials. We report a novel synthesis method for ISO 10993-11 compliant polyamic acid that enables the fabrication of biocompatible polyimide films tailored for neural implants. Using this material, we developed 4 and 32 channel depth and surface electrodes, including custom whole brain ECoG arrays. These were implanted in the laforin knockout mice, a validated model of drug-resistant epilepsy, to monitor spontaneous seizures. Both acute and 12 day recordings demonstrated mechanical flexibility, long term stability, and excellent biocompatibility. This study presents a clinically safe material platform and a complete fabrication pathway for building thin film neural interfaces, paving the way for broader clinical use in applications such as epilepsy monitoring and stereo EEG.

bioengineering↗