@iitrindia.org
Senior Research Fellow
CSIR- Indian Institute of Toxicology Research, Lucknow
Ph.D in Biotechnology from Babasaheb Bhimrao Ambedkar University, Lucknow on the Thesis title " Investigation(s) on the HCMV miRNAs role on cellular Apoptosis" under the supervision of Dr Sunil Babu Gosipatala, Associate Professor, Department of Biotechnology, School of Life Sciences, Babasaheb Bhimrao Ambedkar University Lucknow. I have completed my Masters in Biotechnology from Department of Biotechnology, School of Life Sciences, Babasaheb Bhimrao Ambedkar University Lucknow.
Biochemistry, Genetics and Molecular Biology, Biotechnology, Applied Microbiology and Biotechnology, Neuroscience
Scopus Publications
R. Negi, A. Srivastava, A. K. Srivastava, P. Vatsa, U. A. Ansari, B. Khan, H. Singh, A. Pandeya, and AB Pant
Springer Science and Business Media LLC
Ankita Srivastava, Ankur Kumar Srivastava, Abhishek Pandeya, and Aditya Bhushan Pant
Elsevier BV
R. Negi, A. Srivastava, A. Srivastava, Abhishek Pandeya, P. Vatsa, U. A. Ansari and A. Pant
BACKGROUND AND OBJECTIVES: Induced pluripotent stem cells (iPSCs) derived three-dimensional (3D) model for rare neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) is emerging as a novel alternative to human diseased tissue to explore the disease etiology and potential drug discovery. In the interest of the same, we have generated a TDP-43-mutated human iPSCs (hiPSCs) derived 3D organoid model of ALS disease. The high-resolution mass spectrometry (MS)-based proteomic approach is used to explore the differential mechanism under disease conditions and the suitability of a 3D model to study the disease. MATERIALS AND METHODS: The hiPSCs cell line was procured from a commercial source, grown, and characterized following standard protocols. The mutation in hiPSCs was accomplished using CRISPR/Cas-9 technology and predesigned gRNA. The two groups of organoids were produced by normal and mutated hiPSCs and subjected to the whole proteomic profiling by high-resolution MS in two biological replicates with three technical replicas of each. RESULTS: The proteomic analysis of normal and mutated organoids revealed the proteins associated with pathways of neurodegenerative disorders, proteasomes, autophagy, and hypoxia-inducible factor-1 signaling. Differential proteomic analysis revealed that the mutation in TDP-43 gene caused proteomic deregulation, which impaired protein quality mechanisms. Furthermore, this impairment may contribute to the generation of stress conditions that may ultimately lead to the development of ALS pathology. CONCLUSION: The developed 3D model represents the majority of candidate proteins and associated biological mechanisms altered in ALS disease. The study also offers novel protein targets that may uncloud the precise disease pathological mechanism and be considered for future diagnostic and therapeutic purposes for various neurodegenerative disorders.
Sneha Kumari, Abhishek Pandeya, Raj Kumar Khalko, Ulkarsha, R.C. Sobti, and Sunil Babu Gosipatala
Elsevier
Raj Kumar Khalko, Abhishek Pandeya, Sangeeta Saxena, and Sunil Babu Gosipatala
Informa UK Limited
Human cytomegalovirus (HCMV) is a representative β-herpesvirus that establishes persistent infections in humans, and exhibits high seropositivity rates in adults. It has co-evolved with its human host and employs various strategies to evade antiviral mechanisms by utilizing a significant portion of its genome. HCMV-encoded proteins and miRNAs have been implicated in regulating these mechanisms, enabling viral survival within the human body. During viral infections, autophagy, a conserved catabolic process essential for cellular homeostasis, acts as an antiviral defense mechanism. Multiple studies have reported that HCMV can modulate autophagy through its proteins and miRNAs, thereby influencing its survival within the host. In this study, we showed the potential involvement of HCMV miRNAs in cellular autophagy. We employed various bioinformatic tools to predict putative HCMV miRNAs that target autophagy-related genes and their corresponding cellular autophagy genes. Our results show that the 3'UTR of autophagy-related genes, including ATG9A, ATG9B, ATG16L2, SQSTM1, and EIF2AK2, harbors potential binding sites for hcmv-miR-UL70-3p. Experimental manipulation involving ectopic expression of hcmv-miR-UL70-3p demonstrated a significant reduction in rapamycin-induced autophagy, with ATG9A as its functional target. These findings establish that hcmv-miR-UL70-3p acts as an autophagy inhibitor by suppressing the expression of ATG9A.
Abhishek Pandeya, Raj Kumar Khalko, Bharti Kotarya, Hema, Jitendra Kumar Yadav, Sunil Babu Gosipatala, Sudipta Saha, and R.C. Sobti
CRC Press
Abhishek Pandeya, Raj Kumar Khalko, Sukhveer Singh, Manish Kumar, and Sunil Babu Gosipatala
Public Library of Science (PLoS)
The propensity of viruses to co-opt host cellular machinery by reprogramming the host’s RNA-interference machinery has been a major focus of research, however, regulation of host defense mechanisms by virus-encoded miRNA, is an additional regulatory realm gaining momentum in the arena of host-viral interactions. The Human Cytomegalovirus (HCMV) miRNAs, regulate many cellular pathways alone or in concordance with HCMV proteins, thereby paving a conducive environment for successful infection in the human host. We show that HCMV miRNA, hcmv-miR-UL148D inhibits staurosporine-induced apoptosis in HEK293T cells. We establish that ERN1 mRNA is a bonafide target of hcmv-miR-UL148D and its encoded protein IRE1α is translationally repressed by the overexpression of hcmv-miR-UL148D resulting in the attenuation of apoptosis. Unlike the host microRNA seed sequence (6–8 nucleotides), hcmv-miR-UL148D has long complementarity to 3’ UTR of ERN1 mRNA resulting in mRNA degradation. The repression of IRE1α by the hcmv-miR-UL148D further downregulates Xbp1 splicing and c-Jun N-terminal kinase phosphorylation thus regulating ER-stress and ER-stress induced apoptotic pathways. Strikingly, depletion of ERN1 attenuates staurosporine-induced apoptosis which further suggests that hcmv-miR-UL148D functions through regulation of its target ERN1. These results uncover a role for hcmv-miR-UL148D and its target ERN1 in regulating ER stress-induced apoptosis.
Pranesh Kumar, Mohit Kumar, Anurag Kumar Gautam, Archana Bharti Sonkar, Abhishek Verma, Amita Singh, Raquibun Nisha, Umesh Kumar, Dinesh Kumar, Tarun Mahata,et al.
Elsevier BV
Abhishek Pandeya, Raj Kumar Khalko, Anup Mishra, Nishant Singh, Sukhveer Singh, Sudipta Saha, Sanjay Yadav, Sangeeta Saxena, and Sunil Babu Gosipatala
MDPI AG
Human Cytomegalovirus (HCMV) is a prototypic beta herpesvirus, causing persistent infections in humans. There are medications that are used to treat the symptoms; however, there is no cure yet. Thus, understanding the molecular mechanisms of HCMV replication and its persistence may reveal new prevention strategies. HCMV evasive strategies on the antiviral responses of the human host largely rely on its significant portion of genome. Numerous studies have highlighted the importance of miRNA-mediated regulation of apoptosis, which is an innate immune mechanism that eradicates virus-infected cells. In this study, we explore the antiapoptotic role of hcmv-miR-UL70-3p in HEK293T cells. We establish that hcmv-miR-UL70-3p targets the proapoptotic gene Modulator of Apoptosis-1 (MOAP1) through interaction with its 3’UTR region of mRNA. The ectopic expression of hcmv-miR-UL70-3p mimic significantly downregulates the H2O2-induced apoptosis through the translational repression of MOAP1. Silencing of MOAP1 through siRNA also inhibits the H2O2-induced apoptosis, which further supports the hcmv-miR-UL70-3p mediated antiapoptotic effect by regulating MOAP1 expression. These results uncover a role for hcmv-miR-UL70-3p and its target MOAP1 in regulating apoptosis.
R. C. Sobti, Bharti Kotarya, Abhishek Pandeya, Raj Kumar Khalko, Neelam Yadav, Sudipta Saha, Y. Vasudeva Rao, and Sunil Babu Gosipatala
Springer Singapore
Bharti Kotarya, , Abhishek Pandeya, Raj Kumar Khalko, Anup Mishra, Arti Priyadarshini, N. Vijaya, Manoj Kumar Singh, Sudipta Saha, Sunil Babu Gosipatala,et al.
Journal of Experimental Biology and Agricultural Sciences
Severe Acute Respiratory Syndrome Corona Virus -2 (SARS-CoV-2), puzzled the whole world with its diverse, unique clinical spectrum, and unprecedented transmission dynamics. The disease caused by this virus is named as Coronavirus disease-19 (COVID-19), reported first time in Wuhan, China, in December 2019. It had spread to almost all countries of the world disrupting the health and economy of many countries. It was the recent zoonotic spillover disease reported in humans from the Coronavirus group, without proper medicine and non-existence of prior immunity, this disease posed a challenge to both the scientific and medical fraternity. The search for safe, effective drugs to treat the disease and vaccines against the causative agent SARS- CoV-2 had begun all over the world with public and private partnerships. Many countries are part of the solidarity trail for identifying the effective drugs, clinical trials and vaccines for this global pandemic. Here in this review, we are focussing on the different vaccine production platforms being used in the preparation of vaccines against SARS-CoV-2, their current status and prospects. Vaccine production technology significantly advanced in recent times by imbibing the cutting edge technologies such as nucleic acid based technologies such as DNA/RNA/Codon deoptimization and availability of safe and effective viral vectors produced through rDNA technology. The availability of complete genome sequence of SARS-CoV-2, geared up for the production of vaccine candidates based on these new vaccine production platforms, and in a record time of 4-5 months, these vaccine candidates entered in human clinical trials for the evaluation of safety and efficacy. Prior knowledge on SARS and MERS-CoV’s structural and genomic features, vaccine production platforms used in making vaccines against them greatly augmented in the SARS-CoV-2 vaccine efforts. As per World Health Organization (WHO) a total of202 vaccine candidates are under developing for SARS-CoV-2, among them 47 entered in clinical trials and 156 are in the preclinical stage. These vaccines are prepared by an amalgamation of both new and old traditional vaccine production platforms such as nucleic acid base platforms, inactivated, live attenuated, recombinant viral vectors, protein and peptide-based vaccines. The success of these vaccine candidates lies in the generation of effective immune response for SARS-CoV-2 across all age groups and people with co-morbidities. We briefly summarize the different strategies of SARS-CoV-2 vaccine production and their prospects with an emphasis on different routes of administration and added a basic mathematical model depicting the importance of vaccination for any pandemic.
Sunil G. Babu, Abhishek Pandeya, Neelam Verma, Nikita Shukla, R. Venkatesh Kumar, and Sangeeta Saxena
Springer Science and Business Media LLC