Biology subjects

Babu, V.

Publications and source records attributed to Babu, V..

4 recordsLinked to original sources

bioRxiv2024

Secretome analysis of cancer-associated fibroblasts from prostate cancer to identify potential therapeutic targets

Tumor microenvironment (TME) is a complex entity comprising of several cell types secreted factors as well as an extracellular matrix. A dynamic interaction between tumor cells and their environment profoundly influences tumor survival, aggressiveness, and progression. Cancer- associated fibroblasts (CAFs) are one of the major cellular components of TME and serve as a major source of various secreted factors. These factors are known to modulate tumor survival and progression, as well as their response to therapy. Despite the importance of the TME factors on various aspects of tumor cell behavior, to date factors unique to CAFs that could be potential therapeutic targets are not identified in most systems. This study was aimed at identifying such factors from CAFs which may impact tumor behavior such as the ability to metastasize, response to therapy, relapse, etc. This would aid in identifying therapeutic targets originating from the TME. Furthermore, targeting those factors along with conventional chemotherapeutic drugs is likely to enhance the overall efficacy of the therapy. This study has used fibroblasts derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer for comparing the secretome using a quantitative proteomics approach. 66 proteins unique to CAFs and 24 unique to control (BPH) fibroblasts have been identified. Besides 236 proteins are differentially expressed between control and cancer- associated fibroblasts. Using in-silico approaches the potential processes that may be influenced by the differentially expressed proteins have also been identified. This study has identified both qualitative and quantitative differences between the secretomes of normal and cancer-associated fibroblasts with further validation, this paves the way for identifying therapeutic targets.

cancer biology↗

bioRxiv2024

Comparative transcriptome of normal and cancer- associated fibroblasts

The characteristics of a tumor are largely determined by its interaction with the surrounding micro-environment (TME). TME consists of both cellular and non-cellular components. Cancer associated fibroblasts (CAFs) are a major component of the TME. They are a source of many secreted factors that influence the survival and progression of tumors as well as their response to drugs. Identification of markers either overexpressed in CAFs or unique to CAFs would pave the way for novel therapeutic strategies that would combine conventional chemotherapy and TME-targeted therapy for a better outcome. We have used fibroblast derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer to perform a transcriptome analysis in order to get a comparative profile of normal and cancer-associated fibroblasts. This has identified 818 differentially expressed mRNAs and 17 lincRNAs between normal and cancer-associated fibroblasts.

cancer biology↗

bioRxiv2023

Editing of highly homologous gamma-globin genes by nickase deficient Base Editor mitigates large intergenic deletions

Base editing in gamma-globin promoter is a promising approach for reactivation of fetal-hemoglobin. Recent studies have shown that base editing could result in genotoxic events at the gamma globin locus including 4.9 kb large deletion of intervening region due to nicking in the paralogous HBG1 and HBG2 genes. Although the deletion frequency is less than what is observed with Cas9, it could diminish the therapeutic potential. We sought to evaluate if large deletion could be overcome while maintaining the editing efficiency by replacing the nCas9 of ABE8e with a catalytically inactive deadCas9 (dCas9). Using 3 therapeutically relevant gRNAs targeting the gamma globin promoter, we performed a comprehensive evaluation of the editing outcome and frequency of large deletion using dCas9, nCas9, dCas9-ABE8e and nCas9-ABE8e. Our findings indicate that while nicking in itself induced large deletions, the frequency reduced upon efficient base editing. Notably, there was no appreciable deletion with the use of dCas9-ABE8e making it a safer approach, in terms of genome integrity, for therapeutic genome editing in the gamma-globin locus. Further, we also demonstrate that dCas9 ABE8e can edit efficiently in primary human CD34+ hematopoietic stem and progenitor cells (HSPCs) to achieve therapeutic benefits.

molecular biology↗

bioRxiv2021

In Silico: Mutagenicity and carcinogenicity prediction of Sugar substitutes

Sugar substitutes are mostly artificial, man-made industrial products used as additives in food and beverages. Most of these substances flow through the digestive tract and food chains to become emerging organic contaminants in various abiotic and biotic environmental media. Here, we predict the mutagenicity and carcinogenicity of commonly used sugar substitutes using the in silico based methods. The simplified molecular-input line-entry system (SMILES) of sugar substitutes were obtained from the PubChem database for the toxicity predictions. Here, sixteen sugar substitutes tested out of these four compounds Glucin (GLU), and 5-nitro-2-propoxyaniline (P-4000), SCL, Ace were predicted as mutagens by using in silico tools such as LAZAR, pKCSM, and Toxtree. Based on the predicted results GLU and P-4000 were predicted as carcinogenic sugar substitutes.

bioengineering↗