SP

Dr Sneha M. Pinto


Senior Lecturer in Proteomics
Ph.D.
+44 (0)1483 683409
07 AY 02

Academic and research departments

School of Biosciences.

Publications

Jayshree Advani, Yashwanth Subbannayya, Krishna Patel, Aafaque Ahmad Khan, Arun H. Patil, Ankit P. Jain, Hitendra S. Solanki, Aneesha Radhakrishnan, Sneha M. Pinto, Nandini A. Sahasrabuddhe, Joji K. Thomas, Premendu P. Mathur, Bipin G. Nair, Xiaofei Chang, T.S. Keshava Prasad, David Sidransky, Harsha Gowda, Aditi Chatterjee (2017)Long-Term Cigarette Smoke Exposure and Changes in MiRNA Expression and Proteome in Non-Small-Cell Lung Cancer, In: Omics (Larchmont, N.Y.)21(7)pp. 39-403 Mary Ann Liebert, Inc

Chronic exposure to cigarette smoke markedly increases the risk for lung cancer. Regulation of gene expression at the post-transcriptional level by miRNAs influences a variety of cancer-related interactomes. Yet, relatively little is known on the effects of long-term cigarette smoke exposure on miRNA expression and gene regulation. NCI-H292 (H292) is a cell line sensitive to cigarette smoke with mucoepidermoid characteristics in culture. We report, in this study, original observations on long-term (12 months) cigarette smoke effects in the H292 cell line, using microarray-based miRNA expression profiling, and stable isotopic labeling with amino acids in cell culture-based quantitative proteomic analysis. We identified 112 upregulated and 147 downregulated miRNAs (by twofold) in cigarette smoke-treated H292 cells. The liquid chromatography–tandem mass spectrometry analysis identified 3,959 proteins, of which, 303 proteins were overexpressed and 112 proteins downregulated (by twofold). We observed 39 miRNA target pairs (proven targets) that were differentially expressed in response to chronic cigarette smoke exposure. Gene ontology analysis of the target proteins revealed enrichment of proteins in biological processes driving metabolism, cell communication, and nucleic acid metabolism. Pathway analysis revealed the enrichment of phagosome maturation, antigen presentation pathway, nuclear factor erythroid 2-related factor 2-mediated oxidative stress response, and cholesterol biosynthesis pathways in cigarette smoke-exposed cells. In conclusion, this report makes an important contribution to knowledge on molecular changes in a lung cell line in response to long term cigarette smoke exposure. The findings might inform future strategies for drug target, biomarker and diagnostics innovation in lung cancer, and clinical oncology. These observations also call for further research on the extent to which continuing or stopping cigarette smoking in patients diagnosed with lung cancer translates into molecular and clinical outcomes.

Rajesh Raju, Vishalakshi Nanjappa, Lavanya Balakrishnan, Aneesha Radhakrishnan, Joji Kurian Thomas, Jyoti Sharma, Maozhen Tian, Shyam Mohan Palapetta, Tejaswini Subbannayya, Nirujogi Raja Sekhar, Babylakshmi Muthusamy, Renu Goel, Yashwanth Subbannayya, Deepthi Telikicherla, Mitali Bhattacharjee, Sneha M. Pinto, Nazia Syed, Manda Srinivas Srikanth, Gajanan J. Sathe, Sartaj Ahmad, Sandip N. Chavan, Ghantasala S. Sameer Kumar, Arivusudar Marimuthu, T. S. K. Prasad, H. C. Harsha, B Abdul Rahiman, Osamu Ohara, Gary D. Bader, S. Sujatha Mohan, William P. Schiemann, Akhilesh Pandey (2011)NetSlim: high-confidence curated signaling maps, In: Database : the journal of biological databases and curation2011pp. bar032-bar032 Oxford University Press

We previously developed NetPath as a resource for comprehensive manually curated signal transduction pathways. The pathways in NetPath contain a large number of molecules and reactions which can sometimes be difficult to visualize or interpret given their complexity. To overcome this potential limitation, we have developed a set of more stringent curation and inclusion criteria for pathway reactions to generate high-confidence signaling maps. NetSlim is a new resource that contains this ‘core’ subset of reactions for each pathway for easy visualization and manipulation. The pathways in NetSlim are freely available at http://www.netpath.org/netslim . Database URL: www.netpath.org/netslim

Sneha M. Pinto, Raja Sekhar Nirujogi, Pamela Leal Rojas, Arun H. Patil, Srikanth S. Manda, Yashwanth Subbannayya, Juan Carlos Roa, Aditi Chatterjee, T. S. Keshava Prasad, Akhilesh Pandey (2015)Quantitative phosphoproteomic analysis of IL-33 mediated signaling, In: Proteomics (Weinheim)15(2-3)pp. 532-544

Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines that plays diverse roles in the regulation of immune responses. IL-33 exerts its effects through a heterodimeric receptor complex resulting in the production and release of pro-inflammatory cytokines. A detailed understanding of the signaling pathways activated by IL-33 is still unclear. To gain insights into the IL-33 mediated signaling mechanisms, we carried out a SILAC-based global quantitative phosphoproteomic analysis that resulted in the identification of 7,191 phosphorylation sites derived from 2,746 proteins. We observed alterations in the level of phosphorylation in 1,050 sites corresponding to 672 proteins upon IL-33 stimulation. We report, for the first time, phosphorylation of multiple protein kinases, including Mitogen-activated protein kinase-activated protein kinase 2 (Mapkapk2), Receptor (TNFRSF)-interacting serine-threonine kinase 1 (Ripk1) and NAD kinase (Nadk) that are induced by IL-33. In addition, we observed IL-33-induced phosphorylation of several protein phosphatases including Protein tyrosine phosphatase, Non-receptor type 12 (Ptpn12) and Inositol polyphosphate-5-phosphatase D (Inpp5d), which have not been reported previously. Network analysis revealed an enrichment of actin binding and cytoskeleton reorganization that could be important in macrophage activation induced by IL-33. Our study is the first quantitative analysis of IL-33-regulated phosphoproteome. Our findings significantly expand the understanding of IL-33 mediated signaling events and have the potential to provide novel therapeutic targets pertaining to immune related diseases such as asthma where dysregulation of IL-33 is observed.

Varshasnata Mohanty, Yashwanth Subbannayya, Mohammed Altaf Najar, Sneha M. Pinto, Sandeep Kasaragod, Hilda Karuppiah, Bhuvaragavan Sreeramulu, Kunal Kumar Singh, Sunita Dalal, Shyamjith Manikkoth, Cynthia Arunachalam, Thottethodi Subrahmanya Keshava Prasad, Krishna R. Murthy (2019)Proteomics and Visual Health Research: Proteome of the Human Sclera Using High-Resolution Mass Spectrometry, In: Omics (Larchmont, N.Y.)23(2)pp. 98-110 Mary Ann Liebert, Inc

Eye disorders and resulting visual loss are major public health problems affecting millions of people worldwide. In this context, the sclera is an opaque, thick outer coat covering more than 80% of the eye, and essential in maintaining the shape of the eye and protecting the intraocular contents against infection and the external environment. Despite efforts undertaken to decipher the scleral proteome, the functional and structural picture of the sclera still remain elusive. Recently, proteomics has arisen as a powerful tool that enables identification of proteins playing a critical role in health and disease. Therefore, we carried out an in-depth proteomic analysis of the human scleral tissue using a high-resolution Orbitrap Fusion Tribrid mass spectrometer. We identified 4493 proteins using SequestHT and Mascot as search algorithms in Proteome Discoverer 2.1. Importantly, the proteins, including radixin, synaptopodin, paladin, netrin 1, and kelch-like family member 41, were identified for the first time in human sclera. Gene ontology analysis unveiled that the majority of proteins were localized to the cytoplasm and involved in cell communication and metabolism. In sum, this study offers the largest catalog of proteins identified in sclera with the aim of facilitating their contribution to diagnostics and therapeutics innovation in visual health and autoimmune disorders. This study also provides a valuable baseline for future investigations so as to map the dynamic changes that occur in sclera in various pathological conditions.

Sneha M. Pinto, Yashwanth Subbannayya, D. A. B. Rex, Rajesh Raju, Oishi Chatterjee, Jayshree Advani, Aneesha Radhakrishnan, T. S. Keshava Prasad, Mohan R. Wani, Akhilesh Pandey (2018)A network map of IL-33 signaling pathway, In: Journal of cell communication and signaling12(3)pp. 615-624 Springer Netherlands

Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines that play a central role in the regulation of immune responses. Its release from epithelial and endothelial cells is mediated by pro-inflammatory cytokines, cell damage and by recognition of pathogen-associated molecular patterns (PAMPs). The activity of IL-33 is mediated by binding to the IL-33 receptor complex (IL-33R) and activation of NF-κB signaling via the classical MyD88/IRAK/TRAF6 module. IL-33 also induces the phosphorylation and activation of ERK1/2, JNK, p38 and PI3K/AKT signaling modules resulting in the production and release of pro-inflammatory cytokines. Aberrant signaling by IL-33 has been implicated in the pathogenesis of several acute and chronic inflammatory diseases, including asthma, atopic dermatitis, rheumatoid arthritis and ulcerative colitis among others. Considering the biomedical importance of IL-33, we developed a pathway resource of signaling events mediated by IL-33/IL-33R in this study. Using data mined from the published literature, we describe an integrated pathway reaction map of IL-33/IL-33R consisting of 681 proteins and 765 reactions. These include information pertaining to 19 physical interaction events, 740 enzyme catalysis events, 6 protein translocation events, 4 activation/inhibition events, 9 transcriptional regulators and 2492 gene regulation events. The pathway map is publicly available through NetPath ( http://www.netpath.org /), a resource of human signaling pathways developed previously by our group. This resource will provide a platform to the scientific community in facilitating identification of novel therapeutic targets for diseases associated with dysregulated IL-33 signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_120 .

Riaz Abdulla, Jofy Devasia Puthenpurackal, Sneha M Pinto, Punchappady Devasya Rekha, Yashwanth Subbannayya (2023)Serum autoantibody profiling of oral squamous cell carcinoma patients reveals NUBP2 as a potential diagnostic marker, In: Frontiers in oncology13

Introduction Oral Squamous Cell Carcinoma (OSCC), a common malignancy of the head and neck region, is frequently diagnosed at advanced stages, necessitating the development of efficient diagnostic methods. Profiling autoantibodies generated against tumor-associated antigens have lately demonstrated a promising role in diagnosis, predicting disease course, and response to therapeutics and relapse. Methods In the current study, we, for the first time, aimed to identify and evaluate the diagnostic value of autoantibodies in serum samples of patients with OSCC using autoantibody profiling by an immunome protein array. The utility of anti-NUBP2 antibody and tissue positivity in OSCC was further evaluated. Results and discussion We identified a total of 53 autoantibodies with significant differential levels between OSCC and control groups, including 25 that were increased in OSCC and 28 that were decreased. These included autoantibodies against Thymidine kinase 1 (TK1), nucleotide-binding protein 2 (NUBP2), and protein pyrroline-5-carboxylate reductase 1 (PYCR1), among others. Immunohistochemical validation indicated positive staining of NUBP2 in a large majority of cases (72%). Further, analysis of OSCC data available in TCGA revealed higher NUBP2 expression correlated with better disease-free patient survival. In conclusion, the differential serum autoantibodies identified in the current study, including those for NUBP2, could be used as potential biomarkers for early diagnosis or as screening biomarkers for OSCC pending investigation in a larger cohort.

Additional publications