1. PhD in Biological Science
Distinction
Thesis: Exploring sequence independent functional conservation of lncRNAs
Supervisor: Dr. Vinod Scaria and Dr. Sridhar Sivasubbu
Institute: CSIR-Institute of Genomics & Integrative Biology, New Delhi, India
2. B.Tech in Genetic Engineering
First Class with Distinction
Main topics: Genetic engineering, recombinant technology, genetics, molecular biology
SRM Institute of Science and Technology, Kattankulathur, India
RESEARCH, TEACHING, or OTHER INTERESTS
Biochemistry, Genetics and Molecular Biology, Molecular Medicine, Cardiology and Cardiovascular Medicine, Genetics
15
Scopus Publications
829
Scholar Citations
11
Scholar h-index
11
Scholar i10-index
Scopus Publications
NFATc1 drives Orai3 transcription and proteolysis by harnessing epigenome differences in the MARCH8 promoter Sharon Raju, Akshay Sharma, Sakshi Dahiya, Gyan Ranjan, Rajender K Motiani EMBO Journal, 2025 Several autonomous mechanisms regulate protein expression, such as transcription, translation, post-translational modifications, and epigenetic changes. Rarely, these processes are controlled by the same molecular player with overlapping roles. Here, we reveal that transcription factor NFATc1 regulates both transcription and degradation of the Ca2+ channel Orai3 in a context-dependent manner. We demonstrate that NFATc1 drives Orai3 transcription in non-metastatic pancreatic cancer cells. In invasive and metastatic pancreatic cancer cells, NFATc1 induces Orai3 lysosomal degradation by transcriptionally enhancing MARCH8 E3-ubiquitin ligase. We show that MARCH8 physically interacts with Orai3 intracellular loop eventually resulting in its ubiquitination at the N-terminal. Mechanistically, the dichotomy in the regulation of Orai3 expression emerges from the differences in MARCH8 epigenetic landscape. We uncover that MARCH8 promoter is hyper-methylated in non-metastatic cells. Importantly, we demonstrate that MARCH8 restricts pancreatic cancer metastasis by targeting Orai3 degradation, thereby highlighting the pathophysiological importance of this signaling module. Taken together, we report a unique and clinically relevant scenario wherein the same transcription factor both enhances and curtails the expression of a target protein in cancer.
Development of an In Silico Platform (TRIPinRNA) for the Identification of Novel RNA Intramolecular Triple Helices and Their Validation Using Biophysical Techniques Isha Rakheja, Vishal Bharti, S Sahana, Prosad Kumar Das, Gyan Ranjan, Ajit Kumar, Niyati Jain, Souvik Maiti Biochemistry, 2025 , but the intrigue remains whether it is indeed as rare as it is understood to be or just waiting for a closer look from a new vantage point. TRIPinRNA, our Python-based in silico platform, allows for a comprehensive sequence-pattern search for potential triplex formation in the human transcriptome─noncoding as well as coding. Using this tool, we report the putative occurrence of homopyrimidine type (canonical) triple helices as well as heteropurine-pyrimidine strand type (noncanonical) triple helices in the human transcriptome and validate the formation of both types of triplexes using biophysical approaches. We find that the occurrence of triplex structures has a strong correlation with local GC content, which might be influencing their formation. By employing a search that encompasses both canonical and noncanonical triplex structures across the human transcriptome, this study enriches the understanding of RNA biology. Lastly, TRIPinRNA can be utilized in finding triplex structures for any organism with an annotated transcriptome.
SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function Gyan Ranjan, Paras Sehgal, Vinod Scaria, Sridhar Sivasubbu EMBO Reports, 2024 In this study, we characterize a novel lncRNA-producing gene locus that we name Syntenic Cardiovascular Conserved Region-Associated lncRNA-6 (scar-6) and functionally validate its role in coagulation and cardiovascular function. A 12-bp deletion of the scar-6 locus in zebrafish (scar-6gib007Δ12/Δ12) results in cranial hemorrhage and vascular permeability. Overexpression, knockdown and rescue with the scar-6 lncRNA modulates hemostasis in zebrafish. Molecular investigation reveals that the scar-6 lncRNA acts as an enhancer lncRNA (elncRNA), and controls the expression of prozb, an inhibitor of factor Xa, through an enhancer element in the scar-6 locus. The scar-6 locus suppresses loop formation between prozb and scar-6 sequences, which might be facilitated by the methylation of CpG islands via the prdm14-PRC2 complex whose binding to the locus might be stabilized by the scar-6 elncRNA transcript. Binding of prdm14 to the scar-6 locus is impaired in scar-6gib007Δ12/Δ12 zebrafish. Finally, activation of the PAR2 receptor in scar-6gib007Δ12/Δ12 zebrafish triggers NF-κB-mediated endothelial cell activation, leading to vascular dysfunction and hemorrhage. We present evidence that the scar-6 locus plays a role in regulating the expression of the coagulation cascade gene prozb and maintains vascular homeostasis.
Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments Jyoti Tanwar, Kriti Ahuja, Akshay Sharma, Paras Sehgal, Gyan Ranjan, Farina Sultan, Anushka Agrawal, Donato D’Angelo, Anshu Priya, Vamsi K. Yenamandra, Archana Singh, Anna Raffaello, Muniswamy Madesh, Rosario Rizzuto, Sridhar Sivasubbu, Rajender K. Motiani Plos Biology, 2024 Mitochondria regulate several physiological functions through mitochondrial Ca2+ dynamics. However, role of mitochondrial Ca2+ signaling in melanosome biology remains unknown. Here, we show that pigmentation requires mitochondrial Ca2+ uptake. In vitro gain and loss of function studies demonstrate that mitochondrial Ca2+ uniporter (MCU) is crucial for melanogenesis while MCU rheostat, MCUb negatively control melanogenesis. Zebrafish, MCU+/- and MCUb-/- mice models show that MCU complex drives pigmentation in vivo. Mechanistically, MCU silencing activates transcription factor NFAT2 to induce expression of keratin (5, 7, and 8) filaments. Interestingly, keratin5 in turn augments mitochondrial Ca2+ uptake and potentiates melanogenesis by regulating melanosome biogenesis and maturation. Hence this signaling module acts as a negative feedback loop that fine-tunes both mitochondrial Ca2+ signaling and pigmentation. Notably, mitoxantrone, an FDA approved drug that inhibits MCU, reduces pigmentation thereby highlighting therapeutic potential of targeting mitochondrial Ca2+ uptake for clinical management of pigmentary disorders. Taken together, we reveal an MCU-NFAT2-Keratin5 driven signaling axis that acts as a critical determinant of mitochondrial Ca2+ uptake and pigmentation. Given the vital role of mitochondrial Ca2+ signaling and keratin filaments in cellular physiology, this feedback loop could be operational in a variety of other patho-physiological processes.
Functional long non-coding and circular RNAs in zebrafish Gyan Ranjan, Paras Sehgal, Disha Sharma, Vinod Scaria, Sridhar Sivasubbu Briefings in Functional Genomics, 2021 The utility of model organisms to understand the function of a novel transcript/genes has allowed us to delineate their molecular mechanisms in maintaining cellular homeostasis. Organisms such as zebrafish have contributed a lot in the field of developmental and disease biology. Attributable to advancement and deep transcriptomics, many new transcript isoforms and non-coding RNAs such as long noncoding RNA (lncRNA) and circular RNAs (circRNAs) have been identified and cataloged in multiple databases and many more are yet to be identified. Various methods and tools have been utilized to identify lncRNAs/circRNAs in zebrafish using deep sequencing of transcriptomes as templates. Functional analysis of a few candidates such as tie1-AS, ECAL1 and CDR1as in zebrafish provides a prospective outline to approach other known or novel lncRNA/circRNA. New genetic alteration tools like TALENS and CRISPRs have helped in probing for the molecular function of lncRNA/circRNA in zebrafish. Further latest improvements in experimental and computational techniques offer the identification of lncRNA/circRNA counterparts in humans and zebrafish thereby allowing easy modeling and analysis of function at cellular level.
LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy Paras Sehgal, Samatha Mathew, Ambily Sivadas, Arjun Ray, Jyoti Tanwar, Sushma Vishwakarma, Gyan Ranjan, K V Shamsudheen, Rahul C Bhoyar, Abhishek Pateria, Elvin Leonard, Mukesh Lalwani, Archana Vats, Rajeev R Pappuru, Mudit Tyagi, Saumya Jakati, Shantanu Sengupta, Binukumar B K, Subhabrata Chakrabarti, Inderjeet Kaur, Rajender K Motiani, Vinod Scaria, Sridhar Sivasubbu EMBO Journal, 2021
Rapid and accurate nucleobase detection using FnCas9 and its application in COVID-19 diagnosis Mohd. Azhar, Rhythm Phutela, Manoj Kumar, Asgar Hussain Ansari, Riya Rauthan, Sneha Gulati, Namrata Sharma, Dipanjali Sinha, Saumya Sharma, Sunaina Singh, Sundaram Acharya, Sajal Sarkar, Deepanjan Paul, Poorti Kathpalia, Meghali Aich, Paras Sehgal, Gyan Ranjan, Rahul C. Bhoyar, Khushboo Singhal, Harsha Lad, Pradeep Kumar Patra, Govind Makharia, Giriraj Ratan Chandak, Bala Pesala, Debojyoti Chakraborty, Souvik Maiti Biosensors and Bioelectronics, 2021 Rapid detection of DNA/RNA pathogenic sequences or variants through point-of-care diagnostics is valuable for accelerated clinical prognosis, as witnessed during the recent COVID-19 outbreak. Traditional methods relying on qPCR or sequencing are tough to implement with limited resources, necessitating the development of accurate and robust alternative strategies. Here, we report FnCas9 Editor Linked Uniform Detection Assay (FELUDA) that utilizes a direct Cas9 based enzymatic readout for detecting nucleobase and nucleotide sequences without trans-cleavage of reporter molecules. We also demonstrate that FELUDA is 100% accurate in detecting single nucleotide variants (SNVs), including heterozygous carriers, and present a simple web-tool JATAYU to aid end-users. FELUDA is semi-quantitative, can adapt to multiple signal detection platforms, and deploy for versatile applications such as molecular diagnosis during infectious disease outbreaks like COVID-19. Employing a lateral flow readout, FELUDA shows 100% sensitivity and 97% specificity across all ranges of viral loads in clinical samples within 1hr. In combination with RT-RPA and a smartphone application True Outcome Predicted via Strip Evaluation (TOPSE), we present a prototype for FELUDA for CoV-2 detection closer to home.
Initial Insights Into the Genetic Epidemiology of SARS-CoV-2 Isolates From Kerala Suggest Local Spread From Limited Introductions Chandni Radhakrishnan, Mohit Kumar Divakar, Abhinav Jain, Prasanth Viswanathan, Rahul C. Bhoyar, Bani Jolly, Mohamed Imran, Disha Sharma, Mercy Rophina, Gyan Ranjan, Paras Sehgal, Beena Philomina Jose, Rajendran Vadukkoot Raman, Thulaseedharan Nallaveettil Kesavan, Kalpana George, Sheela Mathew, Jayesh Kumar Poovullathil, Sajeeth Kumar Keeriyatt Govindan, Priyanka Raveendranadhan Nair, Shameer Vadekkandiyil, Vineeth Gladson, Midhun Mohan, Fairoz Cheriyalingal Parambath, Mohit Mangla, Afra Shamnath, , Sridhar Sivasubbu, Vinod Scaria Frontiers in Genetics, 2021 Coronavirus disease 2019 (COVID-19) rapidly spread from a city in China to almost every country in the world, affecting millions of individuals. The rapid increase in the COVID-19 cases in the state of Kerala in India has necessitated the understanding of SARS-CoV-2 genetic epidemiology. We sequenced 200 samples from patients in Kerala using COVIDSeq protocol amplicon-based sequencing. The analysis identified 166 high-quality single-nucleotide variants encompassing four novel variants and 89 new variants in the Indian isolated SARS-CoV-2. Phylogenetic and haplotype analysis revealed that the virus was dominated by three distinct introductions followed by local spread suggesting recent outbreaks and that it belongs to the A2a clade. Further analysis of the functional variants revealed that two variants in the S gene associated with increased infectivity and five variants mapped in primer binding sites affect the efficacy of RT-PCR. To the best of our knowledge, this is the first and most comprehensive report of SARS-CoV-2 genetic epidemiology from Kerala.
NFATc1 drives Orai3 transcription and proteolysis by harnessing epigenome differences in the MARCH8 promoter S Raju, A Sharma, S Dahiya, G Ranjan, RK Motiani The EMBO Journal 44 (21), 6137 , 2025 2025 Citations: 2
Orai3 orchestrates gemcitabine resistance in pancreatic cancer via NFATc1-SLIT3 axis S Arora, A Tanwar, G Ranjan, RK Motiani bioRxiv, 2025.08. 22.671673 , 2025 2025 Citations: 1
Syntenic LncRNA locus exhibits DNA regulatory functions with sequence evolution G Ranjan, V Scaria, S Sivasubbu Gene 933, 148988 , 2025 2025 Citations: 6
Development of an In Silico Platform (TRIPinRNA) for the Identification of Novel RNA Intramolecular Triple Helices and Their Validation Using Biophysical Techniques I Rakheja, V Bharti, S Sahana, PK Das, G Ranjan, A Kumar, N Jain, ... Biochemistry 64 (1), 250-265 , 2024 2024 Citations: 1
Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments J Tanwar, K Ahuja, A Sharma, P Sehgal, G Ranjan, F Sultan, A Agrawal, ... PLoS biology 22 (11), e3002895 , 2024 2024 Citations: 17
SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function G Ranjan, P Sehgal, V Scaria, S Sivasubbu EMBO reports 25 (11), 4950-4978 , 2024 2024 Citations: 1
LncRNA TAAL is a Modulator of Tie1-Mediated Vascular Function in Diabetic Retinopathy G Ranjan, S Arora, S Sharma, L Sharma, RC Bhoyar, V Senthivel, ... bioRxiv , 2024 2024
Functional long non-coding and circular RNAs in zebrafish G Ranjan, P Sehgal, D Sharma, V Scaria, S Sivasubbu Briefings in Functional Genomics 20 (6), 348-360 , 2021 2021 Citations: 8
Asymptomatic reinfection in 2 healthcare workers from India with genetically distinct severe acute respiratory syndrome coronavirus 2 V Gupta, RC Bhoyar, A Jain, S Srivastava, R Upadhayay, M Imran, B Jolly, ... Clinical Infectious Diseases 73 (9), e2823-e2825 , 2021 2021 Citations: 229
LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy P Sehgal, S Mathew, A Sivadas, A Ray, J Tanwar, S Vishwakarma, ... The EMBO journal 40 (15), EMBJ2020107134 , 2021 2021 Citations: 59
Rapid and accurate nucleobase detection using FnCas9 and its application in COVID-19 diagnosis M Azhar, R Phutela, M Kumar, AH Ansari, R Rauthan, S Gulati, N Sharma, ... Biosensors and Bioelectronics 183, 113207 , 2021 2021 Citations: 179
Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions C Radhakrishnan, MK Divakar, A Jain, P Viswanathan, RC Bhoyar, ... Frontiers in genetics 12, 630542 , 2021 2021 Citations: 20
High throughput detection and genetic epidemiology of SARS-CoV-2 using COVIDSeq next-generation sequencing RC Bhoyar, A Jain, P Sehgal, MK Divakar, D Sharma, M Imran, B Jolly, ... PloS one 16 (2), e0247115 , 2021 2021 Citations: 190
Insights from genomes and genetic epidemiology of SARS-CoV-2 isolates from the state of Andhra Pradesh PR Rani, M Imran, JV Lakshmi, B Jolly, S Afsar, A Jain, MK Divakar, ... Epidemiology & Infection 149, e181 , 2021 2021 Citations: 4
Genetic epidemiology of variants associated with immune escape from global SARS-CoV-2 genomes B Jolly, M Rophina, A Shamnath, M Imran, RC Bhoyar, MK Divakar, ... BioRxiv, 2020.12. 24.424332 , 2020 2020 Citations: 16
Asymptomatic reactivation of SARS-CoV-2 in a child with neuroblastoma characterised by whole genome sequencing SP Yadav, D Thakkar, RC Bhoyar, A Jain, T Wadhwa, M Imran, B Jolly, ... IDCases 23, e01018 , 2020 2020 Citations: 13
A rapid and sensitive method to detect SARS-CoV-2 virus using targeted-mass spectrometry P Singh, R Chakraborty, R Marwal, VS Radhakrishan, AK Bhaskar, ... Journal of Proteins and Proteomics 11 (3), 159-165 , 2020 2020 Citations: 58
Knockdown of calcium-binding calb2a and calb2b genes indicates the key regulator of the early development of the zebrafish, Danio rerio RC Bhoyar, AG Jadhao, A Sabharwal, G Ranjan, S Sivasubbu, C Pinelli Brain Structure and Function 224 (2), 627-642 , 2019 2019 Citations: 11
Novel LINS1 missense mutation in a family with non‐syndromic intellectual disability J Sheth, G Ranjan, K Shah, R Bhavsar, F Sheth American journal of medical genetics Part A 173 (4), 1041-1046 , 2017 2017 Citations: 14
MOST CITED SCHOLAR PUBLICATIONS
Asymptomatic reinfection in 2 healthcare workers from India with genetically distinct severe acute respiratory syndrome coronavirus 2 V Gupta, RC Bhoyar, A Jain, S Srivastava, R Upadhayay, M Imran, B Jolly, ... Clinical Infectious Diseases 73 (9), e2823-e2825 , 2021 2021 Citations: 229
High throughput detection and genetic epidemiology of SARS-CoV-2 using COVIDSeq next-generation sequencing RC Bhoyar, A Jain, P Sehgal, MK Divakar, D Sharma, M Imran, B Jolly, ... PloS one 16 (2), e0247115 , 2021 2021 Citations: 190
Rapid and accurate nucleobase detection using FnCas9 and its application in COVID-19 diagnosis M Azhar, R Phutela, M Kumar, AH Ansari, R Rauthan, S Gulati, N Sharma, ... Biosensors and Bioelectronics 183, 113207 , 2021 2021 Citations: 179
LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy P Sehgal, S Mathew, A Sivadas, A Ray, J Tanwar, S Vishwakarma, ... The EMBO journal 40 (15), EMBJ2020107134 , 2021 2021 Citations: 59
A rapid and sensitive method to detect SARS-CoV-2 virus using targeted-mass spectrometry P Singh, R Chakraborty, R Marwal, VS Radhakrishan, AK Bhaskar, ... Journal of Proteins and Proteomics 11 (3), 159-165 , 2020 2020 Citations: 58
Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions C Radhakrishnan, MK Divakar, A Jain, P Viswanathan, RC Bhoyar, ... Frontiers in genetics 12, 630542 , 2021 2021 Citations: 20
Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments J Tanwar, K Ahuja, A Sharma, P Sehgal, G Ranjan, F Sultan, A Agrawal, ... PLoS biology 22 (11), e3002895 , 2024 2024 Citations: 17
Genetic epidemiology of variants associated with immune escape from global SARS-CoV-2 genomes B Jolly, M Rophina, A Shamnath, M Imran, RC Bhoyar, MK Divakar, ... BioRxiv, 2020.12. 24.424332 , 2020 2020 Citations: 16
Novel LINS1 missense mutation in a family with non‐syndromic intellectual disability J Sheth, G Ranjan, K Shah, R Bhavsar, F Sheth American journal of medical genetics Part A 173 (4), 1041-1046 , 2017 2017 Citations: 14
Asymptomatic reactivation of SARS-CoV-2 in a child with neuroblastoma characterised by whole genome sequencing SP Yadav, D Thakkar, RC Bhoyar, A Jain, T Wadhwa, M Imran, B Jolly, ... IDCases 23, e01018 , 2020 2020 Citations: 13
Knockdown of calcium-binding calb2a and calb2b genes indicates the key regulator of the early development of the zebrafish, Danio rerio RC Bhoyar, AG Jadhao, A Sabharwal, G Ranjan, S Sivasubbu, C Pinelli Brain Structure and Function 224 (2), 627-642 , 2019 2019 Citations: 11
Functional long non-coding and circular RNAs in zebrafish G Ranjan, P Sehgal, D Sharma, V Scaria, S Sivasubbu Briefings in Functional Genomics 20 (6), 348-360 , 2021 2021 Citations: 8
Syntenic LncRNA locus exhibits DNA regulatory functions with sequence evolution G Ranjan, V Scaria, S Sivasubbu Gene 933, 148988 , 2025 2025 Citations: 6
Insights from genomes and genetic epidemiology of SARS-CoV-2 isolates from the state of Andhra Pradesh PR Rani, M Imran, JV Lakshmi, B Jolly, S Afsar, A Jain, MK Divakar, ... Epidemiology & Infection 149, e181 , 2021 2021 Citations: 4
NFATc1 drives Orai3 transcription and proteolysis by harnessing epigenome differences in the MARCH8 promoter S Raju, A Sharma, S Dahiya, G Ranjan, RK Motiani The EMBO Journal 44 (21), 6137 , 2025 2025 Citations: 2
Orai3 orchestrates gemcitabine resistance in pancreatic cancer via NFATc1-SLIT3 axis S Arora, A Tanwar, G Ranjan, RK Motiani bioRxiv, 2025.08. 22.671673 , 2025 2025 Citations: 1
Development of an In Silico Platform (TRIPinRNA) for the Identification of Novel RNA Intramolecular Triple Helices and Their Validation Using Biophysical Techniques I Rakheja, V Bharti, S Sahana, PK Das, G Ranjan, A Kumar, N Jain, ... Biochemistry 64 (1), 250-265 , 2024 2024 Citations: 1
SCAR-6 elncRNA locus epigenetically regulates PROZ and modulates coagulation and vascular function G Ranjan, P Sehgal, V Scaria, S Sivasubbu EMBO reports 25 (11), 4950-4978 , 2024 2024 Citations: 1
LncRNA TAAL is a Modulator of Tie1-Mediated Vascular Function in Diabetic Retinopathy G Ranjan, S Arora, S Sharma, L Sharma, RC Bhoyar, V Senthivel, ... bioRxiv , 2024 2024
GRANT DETAILS
1. SERB International travel grant July 2024
International Vascular biology meeting 2024 (IVBM2024), Amsterdam, Netherlands
2. EMBO Fellowship and Flash Talk Oct 2023
EMBO | EMBL Symposium The non-coding genome, EMBL Heidelberg, Germany.
RESEARCH OUTPUTS (PATENTS, SOFTWARE, PUBLICATIONS, PRODUCTS)
a) Designed and developed an In-vitro diagnostic kit for COVID-19 virus detection and licensed it to
commercial companies.
COVIDsure Multiplex Realtime RT-PCR Kit (Licensed to Trivitron Healthcare)
b) Designed and developed TREK/KREC in-vitro diagnostic assay to detect Primary
immunodeficiency diseases (PID) currently in use for screening at Government Medical College,
Kozhikode, Kerala, India.
c) Validated COVIDSeq assay (Illumina) for the first time on suspected SARS CoV-2 patient
samples for the first time.
d) Validated CRISPR-FnCas9 Editor Linked Uniform Detection Assay (FELUDA) for detecting
SNVs, including heterozygous carriers, and diagnosis of COVID-19. (Licensed to Tata MD
Limited)