ORCID Profile
0000-0002-8233-5917
Current Organisations
Macquarie University
,
Garvan Institute of Medical Research
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Publisher: SAGE Publications
Date: 2022
DOI: 10.1177/11786469221126063
Abstract: Autosomal recessive polycystic kidney disease (ARPKD) is an early onset genetic disorder characterized by numerous renal cysts resulting in end stage renal disease. Our study aimed to determine if metabolic reprogramming and tryptophan (Trp) metabolism via the kynurenine pathway (KP) is a critical dysregulated pathway in PKD. Using the Lewis polycystic kidney (LPK) rat model of PKD and Lewis controls, we profiled temporal trends for KP metabolites in plasma, urine, and kidney tissues from 6- and 12-week-old mixed sex animals using liquid and gas chromatography, minimum n = 5 per cohort. A greater kynurenine (KYN) concentration was observed in LPK kidney and plasma of 12-week rats compared to age matched Lewis controls ( P ⩽ .05). LPK kidneys also showed an age effect ( P ⩽ .05) with KYN being greater in 12-week versus 6-week LPK. The metabolites xanthurenic acid (XA), 3-hydroxykynurenine (3-HK), and 3-hydroxyanthranilic acid (3-HAA) were significantly greater in the plasma of 12-week LPK rats compared to age matched Lewis controls ( P ⩽ .05). Plasma XA and 3-HK also showed an age effect ( P ⩽ .05) being greater in 12-week versus 6-week LPK. We further describe a decrease in Trp levels in LPK plasma and kidney (strain effect P ⩽ .05). There were no differences in KP metabolites in urine between cohorts. Using the ratio of product and substrates in the KP, a significant age-strain effect ( P ⩽ .05) was observed in the activity of the KYN/Trp ratio (tryptophan-2,3-dioxygenase [TDO] or indoleamine-2,3-dioxygenase [IDO] activity), kynurenine 3-monooxygenase (KMO), KAT A (kynurenine aminotransferase A), KAT B, total KAT, total KYNU (kynureninase), KYNU A, KYNU B, and total KYNU within LPK kidneys, supporting an activated KP. Confirmation of the activation of these enzymes will require verification through orthogonal techniques. In conclusion, we have demonstrated an up-regulation of the KP in alignment with progression of renal impairment in the LPK rat model, suggesting that KP activation may be a critical contributor to the pathobiology of PKD.
Publisher: Springer New York
Date: 2017
DOI: 10.1007/978-1-4939-7057-5_21
Abstract: Protein microarrays are platforms for studying protein-protein interactions and identifying disease-related self-antigens/autoantigens, which elicit an immune response in a high-throughput format. Protein arrays have been extensively used over the past two decades for several clinical applications. By using this platform, serum containing autoantibodies against potential self-antigens can be screened on proteome-wide arrays, harboring a large repertoire of full-length human proteins. Identification of such autoantigens can help deducing early diagnostic, as well as, prognostic markers in case of malignancies, autoimmune disorders, and other systemic diseases. Here, we provide an overview of the protein microarray technology along with details of an established method to study autoantibody profiles from patient sera.
Publisher: Springer India
Date: 2016
Publisher: Springer India
Date: 2016
Publisher: Springer India
Date: 2016
Publisher: MDPI AG
Date: 05-11-2021
Abstract: The exponential rise in our understanding of the aetiology and pathophysiology of genetic cystic kidney diseases can be attributed to the identification of cystogenic genes over the last three decades. The foundation of this was laid by positional cloning strategies which gradually shifted towards next-generation sequencing (NGS) based screenings. This shift has enabled the discovery of novel cystogenic genes at an accelerated pace unlike ever before and, most notably, the past decade has seen the largest increase in identification of the genes which cause nephronophthisis (NPHP). NPHP is a monogenic autosomal recessive cystic kidney disease caused by mutations in a erse clade of over 26 identified genes and is the most common genetic cause of renal failure in children. NPHP gene types present with some common pathophysiological features alongside a erse range of extra-renal phenotypes associated with specific syndromic presentations. This review provides a timely update on our knowledge of this disease, including epidemiology, pathophysiology, anatomical and molecular features. We delve into the ersity of the NPHP causing genes and discuss known molecular mechanisms and biochemical pathways that may have possible points of intersection with polycystic kidney disease (the most studied renal cystic pathology). We delineate the pathologies arising from extra-renal complications and co-morbidities and their impact on quality of life. Finally, we discuss the current diagnostic and therapeutic modalities available for disease management, outlining possible avenues of research to improve the prognosis for NPHP patients.
Publisher: Springer India
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 15-09-2015
DOI: 10.1038/SREP13895
Abstract: The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum s les and sub-categories of glioblastoma multiforme using Human Proteome chips containing ~17000 full-length human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV s les from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively. Proteins namely, SNX1, EYA1, PQBP1 and IGHG1 showed dysregulation across various grades. Sub-classes of GBM, based on its proximity to the sub-ventricular zone, have been reported to have different prognostic outcomes. To this end, we identified dysregulation of NEDD9, a protein involved in cell migration, with probable prognostic potential. Another subcategory of patients where the IDH1 gene is mutated, are known to have better prognosis as compared to patients carrying the wild type gene. On a comparison of these two cohorts, we found STUB1 and YWHAH proteins dysregulated in Grade II glioma patients. In addition to common pathways associated with tumourigenesis, we found enrichment of immunoregulatory and cytoskeletal remodelling pathways, emphasizing the need to explore biochemical alterations arising due to autoimmune responses in glioma.
Publisher: Impact Journals, LLC
Date: 10-04-2017
Publisher: Mary Ann Liebert Inc
Date: 06-2015
Abstract: Proteomics is at the epicenter of post-genomics biotechnologies that are currently driving the next generation system science. Moreover, proteomics is a truly global science. The 6(th) Annual Meeting of Proteomics Society, India (PSI) and International Conference on "Proteomics from Discovery to Function" held from December 7-9, 2014, was a transformative endeavor for global proteomics, bringing together the luminaries in the field of proteomics for the very first time in India. This meeting report presents the lessons learned and the highlights of this international scientific conference that was comprised of nine thematic sessions, pre- and post-conference workshops, and an opportunity to cultivate enduring collaborations for proteomics science to benefit both India and global society. The conference had an unforgettable impression on the participants: for the first time, India hosted past and present President and Council members from the Human Proteome Organization (HUPO), along with eminent scientists and young scholars from India and abroad in the field of proteomics at such a large scale, a major highlight of this international event. In all, the PSI 2014 was a milestone conference that has firmly poised the Indian life sciences community as a leading contributor to post-genomics life sciences, thus cultivating crucial trans-generational capacity and inspiration by recognizing the emerging scholars and omics systems scientists who can think and conduct science from cell to society.
Publisher: Wiley
Date: 04-2016
Abstract: The complexity involving protein array technology reflects in the fact that instrumentation and data analysis are subject to change depending on the biological question, technical compatibility of instruments and software used in each experiment. Industry has played a pivotal role in establishing standards for future deliberations in sustenance of these technologies in the form of protein array chips, arrayers, scanning devices, and data analysis software. This has enhanced the outreach of protein microarray technology to researchers across the globe. These have encouraged a surge in the adaptation of "nonclassical" approaches such as DNA-based protein arrays, micro-contact printing, label-free protein detection, and algorithms for data analysis. This review provides a unique overview of these industrial solutions available for protein microarray based studies. It aims at assessing the developments in various commercial platforms, thus providing a holistic overview of various modalities, options, and compatibility summarizing the journey of this powerful high-throughput technology.
Publisher: Springer US
Date: 2021
Publisher: Mary Ann Liebert Inc
Date: 04-2016
Publisher: Wiley
Date: 12-09-2016
Abstract: The discovery of DNA microarrays was a major milestone in genomics however, it could not adequately predict the structure or dynamics of underlying protein entities, which are the ultimate effector molecules in a cell. Protein microarrays allow simultaneous study of thousands of proteins eptides, and various advancements in array technologies have made this platform suitable for several diagnostic and functional studies. Antibody arrays enable researchers to quantify the abundance of target proteins in biological fluids and assess PTMs by using the antibodies. Protein microarrays have been used to assess protein-protein interactions, protein-ligand interactions, and autoantibody profiling in various disease conditions. Here, we summarize different microarray platforms with focus on its biological and clinical applications in autoantibody profiling and PTM studies. We also enumerate the potential of tissue microarrays to validate findings from protein arrays as well as other approaches, highlighting their significance in proteomics.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.BBAPAP.2013.12.020
Abstract: Majority of deaths due to communicable and non-communicable diseases occur in the low and middle-income nations (LMNs), mainly due to the lack of early diagnoses and timely treatments. In such a scenario, biomarkers serve as an indispensible resource that can be used as indicators of biological processes, specific disease conditions or response to therapeutic interventions. Evaluation, diagnosis and management of diseases in developing world by following/extrapolating the findings obtained on the basis of the research work involving only the populations from the developed countries, could often be highly misleading due to existence of erse patterns of diseases in developing countries compared to the developed world. Biomarker candidates identified from high-throughput integrated omics technologies have promising potential however, their actual clinical applications are found to be limited, primarily due to the challenges of disease heterogeneity and pre-analytical variability associated with the biomarker discovery pipeline. Additionally, in the developing world, economic crunches, lack of awareness and education, paucity of biorepositories, enormous ersities in socio-epidemiological background, ethnicity, lifestyle, diet, exposure to various environmental risk factors and infectious agents, and ethical and social issues also cumulatively hinder biomarker discovery ventures. Establishment of standard operating procedures, comprehensive data repositories and exchange of scientific findings are crucial for reducing the variability and fragmentation of data. This review highlights the challenges associated with the discovery, validation and translational phases of biomarker research in LMNs with some of their amenable solutions and future prospects. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
Publisher: Cold Spring Harbor Laboratory
Date: 29-03-2023
DOI: 10.1101/2023.03.28.534644
Abstract: While single-cell technologies have allowed scientists to characterize cell states that emerge during cancer progression through temporal s ling, connecting these s les over time and inferring gene-gene relationships that promote cancer plasticity remains a challenge. To address these challenges, we developed TrajectoryNet, a neural ordinary differential equation network that learns continuous dynamics via interpolation of population flows between s led timepoints. By running causality analysis on the output of TrajectoryNet, we compute rich and complex gene-gene networks that drive pathogenic trajectories forward. Applying this pipeline to scRNAseq data generated from in vitro models of breast cancer, we identify and validate a refined CD44 hi EPCAM + CAV1 + marker profile that improves the identification and isolation of cancer stem cells (CSCs) from bulk cell populations. Studying the cell plasticity trajectories emerging from this population, we identify comprehensive temporal regulatory networks that drive cell fate decisions between an epithelial-to-mesenchymal (EMT) trajectory, and a mesenchymal-to-epithelial (MET) trajectory. Through these studies, we identify and validate estrogen related receptor alpha as a critical mediator of CSC plasticity. We further apply TrajectoryNet to an in vivo xenograft model and demonstrate it’s ability to elucidate trajectories governing primary tumor metastasis to the lung, identifying a dominant EMT trajectory that includes elements of our newly-defined temporal EMT regulatory network. Demonstrated here in cancer, the TrajectoryNet pipeline is a transformative approach to uncovering temporal molecular programs operating in dynamic cell systems from static single-cell data.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.JPROT.2015.04.002
Abstract: After a successful completion of the Human Genome Project, deciphering the mystery surrounding the human proteome posed a major challenge. Despite not being largely involved in the Human Genome Project, the Indian scientific community contributed towards proteomic research along with the global community. Currently, more than 76 research/academic institutes and nearly 145 research labs are involved in core proteomic research across India. The Indian researchers have been major contributors in drafting the "human proteome map" along with international efforts. In addition to this, virtual proteomics labs, proteomics courses and remote triggered proteomics labs have helped to overcome the limitations of proteomics education posed due to expensive lab infrastructure. The establishment of Proteomics Society, India (PSI) has created a platform for the Indian proteomic researchers to share ideas, research collaborations and conduct annual conferences and workshops. Indian proteomic research is really moving forward with the global proteomics community in a quest to solve the mysteries of proteomics. A draft map of the human proteome enhances the enthusiasm among intellectuals to promote proteomic research in India to the world.This article is part of a Special Issue entitled: Proteomics in India.
No related grants have been discovered for Shabarni Gupta.