A5068324069- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Gene Regulatory Network Analysis
- Computational Drug Discovery Methods
- Breast Cancer Treatment Studies
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Cell Image Analysis Techniques
- RNA and protein synthesis mechanisms
- Melanoma and MAPK Pathways
- Prostate Cancer Treatment and Research
- Receptor Mechanisms and Signaling
- Genomics and Phylogenetic Studies
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Angiogenesis and VEGF in Cancer
- Histone Deacetylase Inhibitors Research
- Immune cells in cancer
- Estrogen and related hormone effects
- Molecular Biology Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Cancer Immunotherapy and Biomarkers
- Advanced Breast Cancer Therapies
- Ubiquitin and proteasome pathways
Northwestern University
2023-2024
Indian Institute of Science Bangalore
2020-2024
Shanghai Institute for Science of Science
2023
Rajiv Gandhi Centre for Biotechnology
2022
Phenotypic (i.e. non-genetic) heterogeneity in melanoma drives dedifferentiation, recalcitrance to targeted therapy and immunotherapy, consequent tumor relapse metastasis. Various markers or regulators associated with distinct phenotypes have been identified, but, how does a network of interactions among these give rise multiple "attractor" states phenotypic switching remains elusive. Here, we inferred transcription factors (TFs) that act as master for gene signatures diverse cell-states...
Drug resistance and tumor relapse in patients with melanoma is attributed to a combination of genetic non-genetic mechanisms. Dedifferentiation, common mechanism characterized by the loss melanocytic markers. While various molecular attributes de-differentiation have been identified, transition dynamics remain poorly understood. Here, we construct cell-state landscapes, quantify stochastic driving phenotypic switching based on its underlying regulatory network. These landscapes reveal...
Androgen receptor (AR) is considered a marker of better prognosis in hormone positive breast cancers (BC), however, its role triple negative cancer (TNBC) controversial. This may be attributed to intrinsic molecular differences or scoring methods for AR positivity. We derived regulated gene score and examined utility BC subtypes. genes were by applying bioinformatic pipeline on publicly available microarray data sets AR+ cell lines was calculated as average expression six genes. Tumors...
Epithelial to mesenchymal transition (EMT) is a well-studied hallmark of epithelial-like cancers that characterized by loss epithelial markers and gain markers. Melanoma, which derived from melanocytes the skin, also undergo phenotypic plasticity toward mesenchymal-like phenotypes under influence various micro-environmental cues. Our study connects EMT phenomenon de-differentiation (i.e., proliferative more invasive phenotypes) observed in melanoma cells during drug treatment. By analyzing...
Highlights•Luminal signature is closely associated with epithelial in breast cancer•Basal correlates well a hybrid epithelial-mesenchymal signature•Basal cancer exhibits higher heterogeneity patterns•Mathematical modeling of underlying gene networks explains observed heterogeneitySummaryIntra-tumoral phenotypic promotes tumor relapse and therapeutic resistance remains an unsolved clinical challenge. Decoding the interconnections among different biological axes plasticity crucial to...
The innermost layer of the vessel wall is constantly subjected to recurring and relenting mechanical forces by virtue their direct contact with blood flow. Endothelial cells are exposed distension, pressure, shear stress; adaptation these hemodynamic requires significant remodeling cytoskeleton which includes changes in actin, intermediate filaments, microtubules. While much known about effect stress on endothelial actin cytoskeleton; impact microtubule network has not been investigated...
Abstract Spatial transcriptomics provides researchers with a better understanding of gene expression within the tissue context. Although large volumes spatial data have been generated, lack systematic curation and analysis makes reuse challenging. Herein, we present transcriptOmics Analysis Resource (SOAR), resource an extensive, systematically compiled collection across tissues, organs, pathological conditions. SOAR is comprehensive database uniformly processed annotated samples,...
Advanced prostate cancer patients initially respond to hormone therapy, be it in the form of androgen deprivation therapy or second-generation therapies, such as abiraterone acetate enzalutamide. However, most men with eventually develop resistance. This resistance can arise through multiple mechanisms, genetic mutations, epigenetic non-genetic pathways, lineage plasticity along epithelial-mesenchymal neuroendocrine-like axes. These mechanisms often co-exist within a single patient's tumor...
Abstract The anticodon stem of initiator tRNA (i‐tRNA) possesses the characteristic three consecutive GC base pairs (G29:C41, G30:C40, and G31:C39 abbreviated as GC/GC/GC or 3GC pairs) crucial to commencing translation. To understand importance this highly conserved element, we isolated two fast‐growing suppressors Escherichia coli sustained solely on an unconventional i‐tRNA (i‐tRNA cg/GC/cg ) having sequence instead conventional GC/GC/GC. Both have common mutation V93A in initiation factor...
The ribosomal protein uS12 is conserved across all domains of life. Recently, a heterozygous spontaneous mutation in human (corresponding to R49K immediately downstream the universally 44 PNSA47 loop Escherichia coli uS12) was identified for causing ribosomopathy, highlighting importance PNSA loop. To investigate effects similar absence any wild-type alleles, we mutated rpsL gene (encoding E. coli. Consistent with its pathology (in humans), were unable generate support plasmid. However, able...
Abstract Phenotypic (i.e. non-genetic) heterogeneity in melanoma drives dedifferentiation, recalcitrance to targeted therapy and immunotherapy, consequent tumor relapse metastasis. Various markers or regulators associated with distinct phenotypes have been identified, but, how does a network of interactions among these give rise multiple “attractor” states phenotypic switching remains elusive. Here, we inferred transcription factors (TFs) that act as master for gene signatures diverse...
Intra-tumoral phenotypic heterogeneity promotes tumor relapse and therapeutic resistance remains an unsolved clinical challenge. It manifests along multiple axes decoding the interconnections among these different is crucial to understand its molecular origins develop novel strategies control it. Here, we use multi-modal transcriptomic data analysis - bulk, single-cell spatial transcriptomics from breast cancer cell lines primary samples, identify associations between epithelial-mesenchymal...
Abstract Drug resistance and tumor relapse in melanoma patients is attributed to a combination of genetic non-genetic mechanisms. Non-genetic mechanisms drug commonly involve reversible changes the cell-state or phenotype, i.e., alterations molecular profiles that can help cells escape being killed by targeted therapeutics. In melanoma, one most common dedifferentiation, which characterized loss melanocytic markers. While various attributes de-differentiation have been identified, transition...
Summary Epithelial to mesenchymal transition (EMT) is a well-studied hallmark of epithelial-like cancers that characterized by loss epithelial markers and gain markers. Interestingly, melanoma, which derived from melanocytes the skin, also undergo phenotypic plasticity toward mesenchymal-like phenotypes under influence various micro-environmental cues. Our study connects EMT phenomenon de-differentiation (i.e., proliferative more invasive phenotypes) observed in melanoma cells during drug...
Abstract Background Androgen receptor (AR) is considered marker associated with better prognosis within hormone positive tumors. Its role in triple negative tumors however controversial showing both and worse different methods are used for identification of AR driven Conflicting results could be due to intrinsic molecular differences or scoring method positivity. We attempted develop an gene score examined its utility subtypes breast cancer (BC). Methods A bioinformatic pipeline was...
Abstract Background: Epithelial-mesenchymal transition (EMT) phenotype is a complex process and plays central role in tumor progression, aggression, invasion, metastasis, resistance to therapy. Role of androgen receptor (AR) androgens inducing EMT has been well established experimental systems prostate cancer. AR widely expressed all subtypes breast cancer (BC) considered have context dependent based on the steroid hormone microenvironment. Previous studies shown as only sex detectable BC...
Abstract Background The androgen receptor (AR) is an emerging biomarker and favourable therapeutic target in breast cancer (BC), especially Triple negative BC (TNBC) which lacks a targeted treatment shows high molecular heterogeneity. Proportion of AR positive tumours are known to vary (10 43%) within TNBC recent multi-institutional study on TNBC, showed protein status alone not reliable prognostic marker for response. A deeper examination regulated pathways necessary derive gene signatures...
Abstract Quinolone synthase from Aegle marmelos (AmQNS) is a type III polyketide that yields therapeutically effective quinolone and acridone compounds. Based on the high-resolution protein structure of AmQNS, this study provided mechanistic explanation to synthetic selectivity. Additionally, it displays comparatively wide active site entry allows catalytic pocket accommodate bulky substrates, which affects enzyme catalysis. We also develop model framework for comprehending structural...
Abstract Advanced prostate cancer patients initially respond to hormone therapy, be it in the form of androgen deprivation therapy or second-generation therapies, such as abiraterone acetate enzalutamide. However, most men with eventually develop resistance. This resistance emerges several ways, through genetic mutations, epigenetic mechanisms, non-genetic pathways, lineage plasticity along epithelial-mesenchymal neuroendocrine-like axes. These mechanisms often co-exist within a single...
Abstract Small cell lung cancer (SCLC) is a neuroendocrine malignancy with dismal survival rates. Previous studies have revealed inter and intra tumoral heterogeneity of SCLC driven by differentiation multiple gene expression signatures been proposed to classify the distinct molecular subtypes However, few questions remain unanswered: a) how many exist? b) similar or different are these subtypes?, c) which list(s) can be used identify those specific subtypes? Here, we show that irrespective...