Biology subjects

Vij, M.

Publications and source records attributed to Vij, M..

3 recordsLinked to original sources

bioRxiv2025

A workflow using diaPASEF global quantitative proteomic analysis reveals extracellular vesicle biomarker candidates for non-invasive diagnostics in non-small cell lung cancer

Lung cancer is the second most diagnosed cancer in the world. Non-small cell lung cancer is the most common type of lung cancer in the United States. Tissue biopsy is the gold standard for detecting lung cancer but is highly invasive as it necessitates the extraction of a sample of tissue for histologic analysis. It also carries risks of bleeding and/or infection and is inconvenient from a patient perspective. The development of a minimally invasive test, such as one utilizing a blood or urine sample, and capable of providing accurate results for lung cancer detection and/or subtyping, would significantly enhance the clinical landscape and streamline patient care. In this study we utilize A549 and H1299 human lung cancer cell lines, differing in cell type, location within the lung, and genetic composition (Kras & p53 status), and employ diaPASEF for global quantitative proteomic analysis. We demonstrate that extracellular vesicle protein content provides enhanced resolution to differentiate between these two cell lines relative to protein lysate content and reveals alterations in signaling. Protein clusters are identified showing enrichment for distinct biological processes representing multiple gene ontology categories unique to each lung cancer subtype-oxidative phosphorylation, apical junction, and epithelial-mesenchymal transition. We subsequently delineate a short list of urine-detectable protein candidates that is prognostic in a second cohort of lung cancer patients. This list of protein candidates may be useful for the development of a non-invasive test to distinguish between these two subtypes of human lung cancer.

pathology↗

bioRxiv2022

The injury-induced circular RNA circGLIS3 activates dermal fibroblasts to promote wound healing

Delayed skin wound healing and excessive scarring are consequences of an impaired healing process and represent a major health and economic burden worldwide. Current intervention strategies lack efficacy and suffer from high recurrence rates necessitating the investigation into alternative treatment modalities like circular RNAs (circRNAs). By RNA sequencing, we profiled circRNA expression changes during human skin wound healing as well as in keratinocytes and fibroblasts isolated from donor-matched skin and acute wounds. CircGLIS3 was found to be transiently upregulated in the dermal fibroblasts upon skin injury, which was at least partially due to the activated IL-1 signaling. Similarly, overabundant circGLIS3 expression was detected in human keloid lesions compared to the surrounding healthy skin. We found that circGLIS3 resided mainly in the cytoplasm, where it interacted with and stabilized Procollagen C-endopeptidase enhancer 1 (PCPE-1) protein to enhance TGF-{beta} signaling, fibroblast activation, and production of extracellular matrix - important biological processes required for wound repair. Accordingly, knockdown of circGLIS3 in human ex vivo wounds potently reduced wound contraction and delayed re-epithelialization. Collectively, we have identified a previously uncharacterized circRNA regulator of human skin wound healing that may open an avenue for circRNA-based therapeutics for abnormal scarring or nonhealing wounds. One Sentence SummaryTransient increase of the circular RNA circGLIS3 promotes the wound fibroblast activation and extracellular matrix production to facilitate wound closure.

molecular biology↗

bioRxiv2017

Redox-Dependent Condensation Of Mycobacterial Genome By WhiB4

Oxidative stress response in bacteria is generally mediated through coordination between the regulators of oxidant-remediation systems (e.g. OxyR, SoxR) and nucleoid condensation (e.g. Dps, Fis). However, these genetic factors are either absent or rendered nonfunctional in the human pathogen Mycobacterium tuberculosis (Mtb). Therefore, how Mtb organizes genome architecture and regulates gene expression to counterbalance oxidative imbalance during infection is not known. Here, we report that an intracellular redox-sensor, WhiB4, dynamically links genome condensation and oxidative stress response in Mtb. Disruption of WhiB4 affects the expression of genes involved in maintaining redox homeostasis, central carbon metabolism (CCM), respiration, cell wall biogenesis, DNA repair and protein quality control under oxidative stress. Notably, disulfide-linked oligomerization of WhiB4 in response to oxidative stress activates the proteins ability to condense DNA in vitro and in vivo. Further, overexpression of WhiB4 led to hypercondensation of nucleoids, redox imbalance and increased susceptibility to oxidative stress, whereas WhiB4 disruption reversed this effect. In accordance with the findings in vitro, ChIP-Seq data demonstrated non-specific binding of WhiB4 to GC-rich regions of the Mtb genome. Lastly, data indicate that WhiB4 deletion affected the expression of only a fraction of genes preferentially bound by the protein, suggesting its indirect effect on gene expression. We propose that WhiB4 is a novel redox-dependent nucleoid condensing protein that structurally couples Mtbs response to oxidative stress with genome organization and transcription.\n\nSignificance StatementMycobacterium tuberculosis (Mtb) needs to adapt in response to oxidative stress encountered inside human phagocytes. In other bacteria, condensation state of nucleoids modulates gene expression to coordinate oxidative stress response. However, this relation remains elusive in Mtb. We performed molecular dissection of a mechanism controlled by an intracellular redox sensor, WhiB4, in organizing both chromosomal structure and selective expression of adaptive traits to counter oxidative stress in Mtb. Using high-resolution sequencing, transcriptomics, imaging, and redox biosensor, we describe how WhiB4 modulates nucleoid condensation, global gene expression, and redox-homeostasis. WhiB4 over-expression hypercondensed nucleoids and perturbed redox homeostasis whereas WhiB4 disruption had an opposite effect. Our study discovered an empirical role for WhiB4 in integrating redox signals with nucleoid condensation in Mtb.

microbiology↗