Biology subjects

Nair, P.

Publications and source records attributed to Nair, P..

7 recordsLinked to original sources

bioRxiv2026

Scalable generation of human stem cell-derived ureteric bud and collecting duct organoids in stirred bioreactors

Emerging efforts to engineer multicellular kidney tissues for drug discovery, disease modeling, and therapeutic repair require scalable generation of kidney organoids derived from human induced pluripotent stem cells (hiPSCs). Here, we report a method for generating kidney ureteric bud and collecting duct epithelial organoids in stirred tank bioreactors. We demonstrate that extracellular matrix microcarriers facilitate organoid expansion and are compatible with suspension bioreactor methods. The combination of cell-coated matrix microcarriers with stirred bioreactors promotes maturation marker expression compared to static controls comprising matrix-embedded organoids. Our method offers promise for generating epithelial organoids that serve as multicellular models and organ building blocks for scalable biofabrication.

bioengineering↗

bioRxiv2025

Perfusable 3D models of ureteric bud and collecting duct tubules

Recent protocols have emerged to derive ureteric bud (UB) and collecting duct (CD) organoids directly from human induced pluripotent stem cells (hiPSCs). However, these 3D kidney tissues lack biophysical cues from luminal flow and a drainage outlet. To address these limitations, we have created perfusable 3D models of UB and CD tubules. UB organoids are first generated from hiPSCs followed by their dissociation into individual UB cells. Individual UB cells are then seeded onto a 3D perfusable channel embedded within an extracellular matrix composed of fragmented basement membrane matrix and collagen I, where they self-assemble into a confluent monolayer. During in vitro perfusion, these cells exhibit UB-like marker expression over several weeks, during which they undergo budding akin to early branching morphogenesis in developing kidneys. To further promote network formation, UB cells are bioprinted adjacent to a perfusable UB tubule, which form interconnections through luminal fusion. Finally, these 3D perfusable UB tubules are differentiated into collecting duct tubules under luminal flow. Our platform facilitates fundamental understanding of human collecting duct formation during renal development, while paving the way for using these physiologically relevant models for drug testing, disease modeling, and, ultimately, integration into bioprinted kidney tissues for therapeutic use.

bioengineering↗

bioRxiv2025

High-throughput protein target mapping enables accelerated bioactivity discovery for ToxCast and PFAS compounds

Chemical pollution is a global threat to human health, yet the toxicity mechanism of most contaminants remains unknown. Here, we applied an ultrahigh-throughput affinity-selection mass spectrometry (AS-MS) platform to systematically identify protein targets of prioritized chemical contaminants. After benchmarking the platform, we screened 50 human proteins against 481 prioritized chemicals, including 446 ToxCast chemicals and 35 per-and polyfluoroalkyl substances (PFAS). Among 24,050 interactions assessed, we discovered 35 novel interactions involving 14 proteins, with fatty acid-binding proteins (FABPs) emerging as the most ligandable protein family. Given this, we selected FABPs for further validation, which revealed a distinct PFAS binding pattern: legacy PFAS selectively bound to FABP1, whereas replacement compounds, PFECAs, unexpectedly interacted with all FABPs. X-ray crystallography further revealed that the ether group enhances molecular flexibility of alternative PFAS, to accommodate the binding pockets of FABPs. Our findings demonstrate that AS-MS is a robust platform for the discovery of novel protein targets beyond the scope of the ToxCast program and highlight the broader protein-binding spectrum of alternative PFAS as potential regrettable substitutes.

pharmacology and toxicology↗

bioRxiv2021

Radiation-induced reprogramming drives glioma vascular transdifferentiation and tumor recurrence

Treatment-refractory glioma stem and tumor cells exhibit phenotypic plasticity driving recurrence, but the underlying molecular mechanisms remain to be elucidated. Here, we employed single-cell and whole transcriptomic analyses to discover that radiation induces a dynamic shift in functional states of glioma cells allowing for acquisition of vascular endothelial-like and pericyte-like cell phenotypes. These vascular-like cells provide a trophic niche to promote proliferation of irradiated glioma cells, and their selective depletion results in reduced tumor growth post-treatment in vivo. Mechanistically, the acquisition of vascular-like phenotype is driven by increased chromatin accessibility and H3K27 acetylation in specific vascular gene regions post-treatment. Blocking P300 histone acetyltransferase activity reverses the epigenetic changes induced by radiation, and inhibits the phenotypic transition and tumor growth. Our findings highlight an important role for P300 histone acetyltransferase in treatment-induced plasticity and opens a new therapeutic avenue for preventing glioma recurrence. SignificanceOur study demonstrates that radiation therapy promotes glioma resistance by inducing vascular-like phenotypes in GSC that, in turn, aid in proliferation of the remaining tumor cells. This phenotype switch is mediated by P300 HAT, and inhibition of this enzyme is a potential therapeutic target for preventing glioma recurrence following radiation.

cancer biology↗

bioRxiv2018

Absolute quantification of translational regulation and burden using combined sequencing approaches

Translation of mRNAs into proteins is a key cellular process. Ribosome binding sites and stop codons provide signals to initiate and terminate translation, while stable secondary mRNA structures can induce translational recoding events. Fluorescent proteins are commonly used to characterize such elements but require the modification of a parts natural context and allow only a few parameters to be monitored concurrently. Here, we develop an approach that combines ribosome profiling (Ribo-seq) with quantitative RNA sequencing (RNA-seq) to enable the high-throughput characterization of genetic parts controlling translation in absolute units. We simultaneously measure 743 translation initiation rates and 746 termination efficiencies across the Escherichia coli transcriptome, in addition to translational frameshifting induced at a stable RNA pseudoknot structure. By analyzing the transcriptional and translational response, we discover that sequestered ribosomes at the pseudoknot contribute to a {sigma}32-mediated stress response, codon-specific pausing, and a drop in translation initiation rates across the cell. Our work demonstrates the power of integrating global approaches towards a comprehensive and quantitative understanding of gene regulation and burden in living cells.

synthetic biology↗

bioRxiv2018

Inhibition of CaOx crystals by Neolamarckia cadamba: An in vivo approach

The objective of the study was to find out the effectiveness of the methanol fruit extract of N. cadamba on calcium oxalate induced nephrolithiasis in wistar albino rats. Animals were divided into nine groups (n=4) in which group 1 as control, group II as antilithiatic control and group III as lithiatic control. Dose for the methanol fruit extract was selected for the study as 200 and 400mg/kg body weight of fruit extract. Group IV and V were considered as post treatment groups and group VI to IX were co treatment groups. Ethylene glycol in drinking water was given to group II - IX for the induction of renal calculi. All the stone forming constituents such as urea, uric acid and creatinine were reduced significantly (p<0.01) in the extract treated groups. Calcium, oxalate and phosphorous concentrations in kidney were found to be diminished by the supplementation of extract. ICP-MS analysis, Histopathology, microcrystal study and pizzalatos staining confirmed the efficacy of the fruit extract. In conclusion, the results suggested that the fruit extract is endowed with the property of an antilithiatic drug.

pharmacology and toxicology↗

bioRxiv2017

Identification Of A Native Novel Oncolytic Immunoglobulin On Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera Of IgA/IgG

Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5M- 5.0 M and 5.0M-8.0M range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.

cell biology↗