Cancer Research, Cognitive Neuroscience, General Biochemistry, Genetics and Molecular Biology, Structural Biology
75
Scopus Publications
1507
Scholar Citations
22
Scholar h-index
41
Scholar i10-index
Scopus Publications
Muscle Rev-erb controls time-dependent adaptations to chronic exercise in mice Jidong Liu, Fang Xiao, Abhinav Choubey, Udhaya Kumar S, Yanxiang Wang, et al. Nature Communications, 2025 The best time of the day for chronic exercise training and the mechanism underlying the timing effects is unclear. Here, we show that low-intensity, low-volume treadmill training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance. Baseline muscle performance also exhibits diurnal variations, with higher strength but lower endurance before sleep than after waking. Muscle-specific knockout of circadian clock genes Rev-erbα/β (Rev-MKO) in male mice eradicates the diurnal variations in both training and baseline conditions without affecting muscle mass, mitochondrial content, food intake, or spontaneous activities. Multi-omics and metabolic measurements reveal that Rev-erb suppresses fatty acid oxidation and promotes carbohydrate metabolism before sleep. Thus, the muscle-autonomous clock, not feeding or locomotor behaviors, dictates diurnal variations of muscle functions and time-dependent adaptations to training, which has broad implications in metabolic disorders and sports medicine as Rev-erb agonists are exercise mimetics or enhancers. Here, the authors show that low-intensity exercise training in mice before sleep yields greater benefits than after waking for muscle contractile performance and systemic glucose tolerance, a phenomenon abolished by muscle-specific knockout of circadian clock genes Rev-erbα/β.
Transcriptomic profiling and bioinformatics-driven statistical prioritization of CRC biomarkers: A step toward precision oncology Rawdhah M. Saleh, Reham Mansour, Heba A. Almaghrbi, Udhaya Kumar. S, Anju Surendranath, Ala-Eddin Al Moustafa, Alsamman M. Alsamman, Hatem Zayed Gene, 2025 BACKGROUND: Colorectal adenocarcinoma (COAD) is among the most common causes of cancer-related death globally. Early detection and targeted therapy depend on identifying key molecular biomarkers that drive tumor progression. The molecular heterogeneity of COAD demands robust computational strategies to improve the accuracy of biomarker discovery. METHODS: We developed and implemented a comprehensive, multi-step bioinformatics and statistical pipeline to systematically prioritize clinically relevant biomarkers in COAD. This pipeline integrated differential gene expression analysis, protein-protein interaction (PPI) network construction, and functional enrichment analysis to identify key hub genes associated with tumor progression. We subsequently applied principal component analysis (PCA) and overall survival modeling to evaluate the diagnostic and prognostic relevance of these candidates. Receiver operating characteristic (ROC) curve analysis was used to assess their sensitivity and specificity. Finally, experimental validation of the prioritized hub genes was conducted via qPCR across three CRC cell lines (LoVo, HCT-116, and HT-29), confirming their upregulation and supporting their clinical potential. RESULTS: Our integrative pipeline prioritized five key hub genes (CDH3, CXCL1, MMP1, MMP3, and TGFBI) as significantly upregulated in COAD tissues compared to normal controls. Functional enrichment analysis linked these genes to extracellular matrix degradation, epithelial-mesenchymal transition (EMT), inflammatory signaling, and tumor invasion, underscoring their roles in key oncogenic processes. Survival analysis revealed varying degrees of association with patient prognosis, most notably for CXCL1. Diagnostic performance, assessed by ROC analysis, yielded moderate AUC values (0.669-0.692), supporting their potential as biomarkers. Finally, qPCR validation across three CRC cell lines confirmed robust upregulation of all five genes, reinforcing their biological relevance in COAD progression. CONCLUSION: Our study establishes a reproducible, integrative bioinformatics and statistical framework for the systematic identification of clinically actionable biomarkers in CRC. The five hub genes prioritized (CDH3, CXCL1, MMP1, MMP3, and TGFBI) demonstrated consistent diagnostic and prognostic value, offering a solid basis for the development of non-invasive molecular diagnostics and contributing to precision oncology.
Multi-omics delineate growth factor network underlying exercise effects in an Alzheimer's mouse model Xin Li, Chaozhong Liu, Wenbo Li, Guantong Qi, Yanwan Dai, Chaohao Gu, Yuxiang Sun, Wenjun Zhou, Veronica C. Ciliberto, Jing Liang, Udhaya Kumar S, Dongyin Guan, Zhaoyong Hu, Hui Zheng, Zhandong Liu, Hu Chen, Ying‐Wooi Wan, Zheng Sun Alzheimer S and Dementia, 2025 INTRODUCTIONPhysical exercise is a primary defense against age‐related cognitive decline and Alzheimer's disease (AD).METHODSWe conducted single‐nucleus transcriptomic and chromatin accessibility analyses (snRNA‐seq and snATAC‐seq) on the hippocampus of mice carrying mutations in the amyloid precursor protein gene (APPNL‐G‐F) following prolonged voluntary wheel‐running exercise.RESULTSExercise mitigates amyloid‐induced changes in transcriptome and chromatin accessibility through cell type–specific regulatory networks converging on growth factor signaling, particularly the epidermal growth factor receptor (EGFR) signaling. The beneficial effects of exercise on neurocognition can be blocked by pharmacological inhibition of EGFR and its downstream PI3K signaling. Exercise leads to elevated levels of heparin‐binding EGF (HB‐EGF), and intranasal administration of HB‐EGF enhances memory function in sedentary APPNL‐G‐F mice.DISCUSSIONThese findings offer a panoramic delineation of cell type–specific hippocampal transcriptional networks activated by exercise and suggest EGFR signaling as a druggable contributor to exercise‐induced memory enhancement to combat AD‐related cognitive decline.Highlights snRNA‐seq and snATAC‐seq analysis of APPNL‐G‐F mice after prolonged wheel‐running. Exercise counteracts amyloid‐induced transcriptomic and accessibility changes. Networks converge on the activation of EGFR and insulin signaling. Pharmacological inhibition of EGFR and PI3K blocked cognitive benefits of exercise. Intranasal HB‐EGF administration enhances memory in sedentary APPNL‐G‐F mice.
Editorial: Cell cycle modulators: regulating the basic unit of life for disease treatment and tissue regeneration Roberta Giordo, Audra N. Iness, Udhaya Kumar Frontiers in Pharmacology, 2025 induces oxidative stress, while dasatinib, a tyrosine kinase inhibitor, disrupts cancer cell signaling.The combination of these agents results in enhanced cell cycle arrest and induction of oxieptosis, a form of regulated cell death driven by oxidative stress. This study not only highlights the potential of combinatory therapies in overcoming resistance but also advocates for the inclusion of natural compounds in therapeutic regimens. Future research could focus on optimizing dosage and delivery methods to maximize efficacy while minimizing adverse effects.In their exploration of colorectal cancer (CRC), Aljuhani et al. (2024) focus on somatic mutations in BRAF, KRAS, and NRAS, key genes implicated in tumorigenesis. Using massively parallel sequencing, the study identifies actionable oncogenic variants and classifies them based on their therapeutic potential. These mutations appear to be not only CRC biomarkers but also important targets for therapeutic approaches in precision medicine. The authors emphasize the variation in mutation prevalence among populations, highlighting the need for focalized studies to develop customized treatments. By integrating genomic data with clinical outcomes, this research study bridges the gap between molecular biology and personalized medicine, offering a roadmap for future investigations into CRC-targeted therapies.An abnormal arrest of cell cycle was observed by Wang et al.'s (2023) following chronic exposure to methamphetamine (METH) in hippocampal-derived neurospheres. In addition, METH caused abnormal differentiation, enhanced oxidative stress, and apoptosis in both neurons and astrocytes.These findings suggest that METH can disrupt the balance between proliferation and differentiation in neural progenitor cells, potentially leading to long-term cognitive and behavioral deficits. This study provides a framework for understanding METH-induced neurotoxicity's cellular basis and highlights the importance of developing interventions to mitigate its impact on neurogenesis. Moreover, the employment of neurospheres as a model system highlights their utility in studying the effects of environmental toxins on neural development.Fibrotic conditions such as keloids present significant challenges in clinical management due to their persistent and progressive nature. The work by Wang et al. (2024) provides a comprehensive review of the roles of matrix metalloproteinases (MMPs) 2 and 9 in the pathogenesis of keloids.These enzymes, involved in extracellular matrix (ECM) remodeling, are shown to interact with various signaling pathways to promote fibrosis. The authors discuss potential molecular targets exploitable in modulating MMP activity, including inhibitors that can prevent excessive scarring. This review not only consolidates existing knowledge but also identifies gaps that warrant further investigation, such as the interplay between MMPs and immune responses. This study's implications extend beyond keloids, offering insights into other fibrotic diseases and potential therapeutic strategies.Taken together, the studies featured in this Research Topic highlight the intricate interplay between molecular mechanisms and disease progression. From targeting specific oncogenic mutations to understanding the cellular impact of environmental toxins, these contributions underscore the importance of integrating basic and translational research. The emphasis on combination therapies, as demonstrated in the HCC study, reflects a growing recognition of the need for multi-pronged approaches in tackling complex diseases.One of the recurring themes in these studies is the role of oxidative stress in disease pathology.Whether it is the induction of apoptosis in cancer cells or the disruption of neural progenitor cell function, oxidative stress emerges as a double-edged sword-a target for therapeutic intervention and a contributor to disease progression. Such an aspect highlights the need for a fine understanding of redox biology in the context of health and disease.Translating these findings into clinical practice is another critical aspect that needs further exploration. In fact, while the studies provide compelling preclinical evidence, challenges remain
A new horizon in the phosphorylated sites of AGA: the structural impact of C163S mutation in aspartylglucosaminuria through molecular dynamics simulation Ambritha Balasundaram, Sriroopreddy Ramireddy, Udhaya Kumar S., Thirumal Kumar D., Iftikhar Aslam Tayubi, Hatem Zayed, George Priya Doss C. Journal of Biomolecular Structure and Dynamics, 2024 Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by insufficient aspartylglucosaminidase (AGA) activity leading to chronic neurodegeneration. We utilized the PhosphoSitePlus tool to identify the AGA protein's phosphorylation sites. The phosphorylation was induced on the specific residue of the three-dimensional AGA protein, and the structural changes upon phosphorylation were studied via molecular dynamics simulation. Furthermore, the structural behaviour of C163S mutation and C163S mutation with adjacent phosphorylation was investigated. We have examined the structural impact of phosphorylated forms and C163S mutation in AGA. Molecular dynamics simulations (200 ns) exposed patterns of deviation, fluctuation, and change in compactness of Y178 phosphorylated AGA protein (Y178-p), T215 phosphorylated AGA protein (T215-p), T324 phosphorylated AGA protein (T324-p), C163S mutant AGA protein (C163S), and C163S mutation with Y178 phosphorylated AGA protein (C163S-Y178-p). Y178-p, T215-p, and C163S mutation demonstrated an increase in intramolecular hydrogen bonds, leading to greater compactness of the AGA forms. Principle component analysis (PCA) and Gibbs free energy of the phosphorylated/C163S mutation structures exhibit transition in motion/orientation than Wild type (WT). T215-p may be more dominant among these than the other studied phosphorylated forms. It might contribute to hydrolyzing L-asparagine functioning as an asparaginase, thereby regulating neurotransmitter activity. This study revealed structural insights into the phosphorylation of Y178, T215, and T324 in AGA protein. Additionally, it exposed the structural changes of the C163S mutation and C163S-Y178-p of AGA protein. This research will shed light on a better understanding of AGA's phosphorylated mechanism.Communicated by Ramaswamy H. Sarma.
Analysis of signaling cascades from myeloma cells treated with pristimerin Heba Almaghrbi, Rehab Elkardawy, S. Udhaya Kumar, Shilpa Kuttikrishnan, Taghreed Abunada, Manoj Kumar Kashyap, Aamir Ahmad, Shahab Uddin, C. George Priya Doss, Hatem Zayed Advances in Protein Chemistry and Structural Biology, 2023
Mutations in ARSB in MPS VI patients in India Juby Mathew, Sujatha M. Jagadeesh, Meenakshi Bhat, S. Udhaya Kumar, Saravanamuthu Thiyagarajan, Sudha Srinivasan Molecular Genetics and Metabolism Reports, 2015
RECENT SCHOLAR PUBLICATIONS
Intermittent AP-1 activation in muscles contributes to exercise-induced health benefits A Choubey, T Yang, J Jager, S Hong, M Damle, H Yin, R Zhao, C Song, ... bioRxiv , 2026 2026
Muscle Rev-erb controls time-dependent adaptations to chronic exercise in mice J Liu, F Xiao, A Choubey, U Kumar S, Y Wang, S Hong, T Yang, HG Otlu, ... Nature communications 16 (1), 5708 , 2025 2025 Citations: 5
Transcriptomic profiling and bioinformatics-driven statistical prioritization of CRC biomarkers: A step toward precision oncology RM Saleh, RM Kamal, HA Almaghrbi, U Kumar S, A Surendranath, ... Gene 964, 149594 , 2025 2025 Citations: 5
Multi‐omics delineate growth factor network underlying exercise effects in an Alzheimer's mouse model X Li, C Liu, W Li, G Qi, Y Dai, C Gu, Y Sun, W Zhou, VC Ciliberto, J Liang, ... Alzheimer's & Dementia 21 (3), e70024 , 2025 2025 Citations: 1
Cell cycle modulators: regulating the basic unit of life for disease treatment and tissue regeneration R Giordo, AN Iness, U Kumar Frontiers in Pharmacology 16, 1554529 , 2025 2025
Biosynthesis of bioactive pigment from halotolerant Bacillus cereus for fabric – an eco-friendly initiative PAT Mary, KV Gayathri, PS Kumar, R Rajagopal, R Kavitha, U Kumar. S, ... Biomass Conversion and Biorefinery 14 (20), 25479-25493 , 2024 2024 Citations: 2
Unraveling the intricate physiological processes dysregulated in CHD-affected and Dan-Lou tablet-treated individuals A Datta, N George, T Koppolu, U Kumar. S, R Bithia, H Zayed, GP Doss. C Computational Biology and Chemistry 112, 108151 , 2024 2024 Citations: 2
Decoding genetic and pathophysiological mechanisms in amyotrophic lateral sclerosis and primary lateral sclerosis: A comparative study of differentially expressed genes and … H Cathryn R, A Datta, U Kumar S, H Zayed, T Kumar D, GP Doss C Advances in Protein Chemistry and Structural Biology Volume 141, 177-201 , 2024 2024 Citations: 1
Exploring the effect of disease causing mutations in metal binding sites of human ARSA in metachromatic leukodystrophy NM Priya, NS Kumar, SU Kumar, G Mohanraj, R Magesh, H Zayed, ... Advances in Protein Chemistry and Structural Biology 141, 203-221 , 2024 2024 Citations: 3
Effect of biogenic selenium nanocomposite on Okra and metagenomic analysis of bacterial community associated with rhizosphere and phyllosphere JMI Sonali, KV Gayathri, PS Kumar, G Rangasamy, CS Poorva, SU Kumar, ... Waste and Biomass Valorization 15 (3), 1819-1831 , 2024 2024 Citations: 4
Exploring the effect of disease causing mutations in metal binding sites of human ARSA in metachromatic leukodystrophy N Sidharth Kumar, S Udhaya Kumar, G Mohanraj, R Magesh, H Zayed, ... Advances in Protein Chemistry and Structural Biology 141, 203-221 , 2024 2024
The targeted next-generation sequence revealed SMAD4, AKT1, and TP53 mutations from circulating cell-free DNA of breast cancer and its effect on protein structure–A … A Balasundaram, U Kumar. S, A Anil Dedge, G R, SS K, S R, GPD C Journal of Biomolecular Structure and Dynamics 41 (24), 15584-15597 , 2023 2023 Citations: 7
Identification of Potential Inhibitors Targeting GTPase-Kirsten RAt Sarcoma Virus (K-Ras) Driven Cancers via E-Pharmacophore-Based Virtual Screening and Drug Repurposing Approach U Kumar. S, RP Varghese, VA Preethi, CGP Doss, H Zayed Frontiers in Bioscience-Landmark 28 (11), 288 , 2023 2023 Citations: 14
Repurposing drugs: an empowering approach to drug discovery and development S Kumar, V Roy Drug Research 73 (09), 481-490 , 2023 2023 Citations: 34
Exome sequence analysis of rare frequency variants in Late-Onset Alzheimer Disease S Sundarrajan, A Venkatesan, U Kumar S, M Gopikrishnan, IA Tayubi, ... Metabolic Brain Disease, 12 , 2023 2023 Citations: 10
SARS-CoV-2 vaccine breakthrough infections (VBI) by Omicron variant (B. 1.1. 529) and consequences in structural and functional impact Z Abduljaleel, S Melebari, M Athar, S Dehlawi, SU Kumar, SA Aziz, ... Cellular Signalling 109, 110798 , 2023 2023 Citations: 5
Molecular dynamics simulations corroborate recombinant expression studies carried out on three αIIb β‐propeller mutations reported in Indian Glanzmann thrombasthenia patients FP Chandrasekaran, A Vishal, U Arora, U Kumar S, PD George C, ... Journal of Cellular Biochemistry 124 (7), 989-1001 , 2023 2023 Citations: 3
A new horizon in the phosphorylated sites of AGA: the structural impact of C163S mutation in aspartylglucosaminuria through molecular dynamics simulation A Balasundaram, S Ramireddy, U Kumar S, IA Tayubi, H Zayed Journal of Biomolecular Structure and Dynamics, 1-12 , 2023 2023
Gene network interaction analysis to elucidate the antimicrobial resistance mechanisms in the Clostridium difficile M Anusha, V Tejaswini, SU Kumar, CN Prashantha, K Vasudevan, ... Microbial Pathogenesis 178, 106083 , 2023 2023 Citations: 16
Integrated gene network analysis sheds light on understanding the progression of Osteosarcoma H Dey, K Vasudevan, GPD C, KS Udhaya, A El Allali, AM Alsamman, ... Frontiers in Medicine 10, 664 , 2023 2023 Citations: 5
MOST CITED SCHOLAR PUBLICATIONS
The Rise and Impact of COVID-19 in India SU Kumar, DT Kumar, BP Christopher, C Doss Frontiers in Medicine 7, 250 , 2020 2020 Citations: 215
Analysis of differentially expressed genes and molecular pathways in familial hypercholesterolemia involved in atherosclerosis: A systematic and bioinformatics approach HZ Udhaya Kumar S, Thirumal Kumar D, Bithia R, Srivarshini Sankar, Magesh R ... Frontiers in Genetics 11 (734) , 2020 2020 Citations: 132
Integrative bioinformatics approaches to map potential novel genes and pathways involved in ovarian cancer U Kumar S, T Kumar D, R Siva, H George Priya Doss C and Zayed Frontiers in Bioengineering and Biotechnology 7, 391 , 2019 2019 Citations: 86
Dysregulation of signaling pathways due to differentially expressed genes from the B-cell transcriptomes of systemic lupus erythematosus patients- a bioinformatics approach U Kumar S, T Kumar. D, R Siva, GP Doss C, S Younes, N Younes, ... Frontiers in Bioengineering and Biotechnology 8 (276) , 2020 2020 Citations: 71
CDK regulators—Cell cycle progression or apoptosis—Scenarios in normal cells and cancerous cells M D'costa, A Bothe, S Das, SU Kumar, R Gnanasambandan, CGP Doss Advances in Protein Chemistry and Structural Biology , 2023 2023 Citations: 57
A review of bioinformatics tools and web servers in different microarray platforms used in cancer research RH Cathryn, SU Kumar, SalmaYounes, H Zayed, CGP Doss Advances in Protein Chemistry and Structural Biology 131, 85-164 , 2022 2022 Citations: 46
Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity U Kumar S, B Rajan, T Kumar D, A Preethi V, T Abunada, S Younes, ... Genes 11 (1256), 1-19 , 2020 2020 Citations: 45
Molecular dynamics, residue network analysis, and cross-correlation matrix to characterize the deleterious missense mutations in GALE causing galactosemia III SU Kumar, S Sankar, DT Kumar, S Younes, N Younes, R Siva, CGP Doss, ... Cell Biochemistry and Biophysics 79 (2), 201-219 , 2021 2021 Citations: 42
Mutational landscape of K-Ras substitutions at 12th position-a systematic molecular dynamics approach S Udhaya Kumar, R Bithia, D Thirumal Kumar, CGP Doss, H Zayed Journal of biomolecular structure & dynamics 40 (4), 1571-1585 , 2020 2020 Citations: 38
Network analysis of transcriptomics data for the prediction and prioritization of membrane-associated biomarkers for idiopathic pulmonary fibrosis (IPF) by bioinformatics approach S Mishra, MI Shah, SU Kumar, DT Kumar, C Gopalakrishnan, ... Advances in Protein Chemistry and Structural Biology 123, 241-273 , 2020 2020 Citations: 36
Oxidation of 5-hydroxymethylfurfural to 5-formyl furan-2-carboxylic acid by non-precious transition metal oxide-based catalyst P Pal, S Kumar, MM Devi, S Saravanamurugan The Journal of Supercritical Fluids 160, 104812 , 2020 2020 Citations: 35
Repurposing drugs: an empowering approach to drug discovery and development S Kumar, V Roy Drug Research 73 (09), 481-490 , 2023 2023 Citations: 34
A systemic approach to explore the mechanisms of drug resistance and altered signaling cascades in extensively drug-resistant tuberculosis SU Kumar, A Saleem, DT Kumar, VA Preethi, S Younes, H Zayed, ... Advances in Protein Chemistry and Structural Biology 127, 343-364 , 2021 2021 Citations: 34
Computational investigation to identify potent inhibitors of the GTPase-Kirsten RAt sarcoma virus (K-Ras) mutants G12C and G12D SU Kumar, CGP Doss Computers in Biology and Medicine 139, 104946 , 2021 2021 Citations: 31
An extensive computational approach to analyze and characterize the functional mutations in the galactose-1-phosphate uridyl transferase (GALT) protein responsible for … U Kumar S, T Kumar D, R Siva, GP Doss C, H Zayed Computers in Biology and Medicine 117 (103583) , 2019 2019 Citations: 31
Comprehensive in silico screening and molecular dynamics studies of missense mutations in Sjogren-Larsson syndrome associated with the ALDH3A2 gene SU Kumar, DT Kumar, PD Mandal, S Sankar, R Haldar, B Kamaraj, ... Advances in Protein Chemistry and Structural Biology 120 (3), 215 , 2020 2020 Citations: 25
A computational model revealing the immune-related hub genes and key pathways involved in rheumatoid arthritis (RA) A Balasundaram, SU Kumar, CGP Doss Advances in Protein Chemistry and Structural Biology 129, 247-273 , 2022 2022 Citations: 24
Structure-Based Virtual Screening to Identify Novel Potential Compound as an Alternative to Remdesivir to Overcome the RdRp Protein Mutations in SARS-CoV-2 T Kumar, N Shaikh, U Kumar, GP Doss, H Zayed Frontiers in Molecular Biosciences 8 (213), 645216 , 2021 2021 Citations: 24
Mutations in ARSB in MPS VI patients in India SS Mathew J, Jagadeesh SM, Bhat M, Udhaya Kumar S, Thiyagarajan S Molecular Genetics and Metabolism Reports 4, 53-61 , 2015 2015 Citations: 24
A review of novel coronavirus disease (COVID-19): based on genomic structure, phylogeny, current shreds of evidence, candidate vaccines, and drug repurposing SU Kumar, SR Nithya, P Kannan, N Jain, DT Kumar, R Magesh, S Younes, ... 3 Biotech 11 (No.198), 1-22 , 2021 2021 Citations: 22
GRANT DETAILS
I have been awarded the "Frank Belton Kimmel and Sandra Kimmel Endowed Post-Doctoral Trainee Fellowship for Diabetes Research" by Baylor College of Medicine (2023-2025). Recently, I have been awarded a Postdoctoral Fellowship in Training Program in Precision Environmental Health Sciences (TPEHS), funded by NIH-NIEHS (T32) and Gulf Coast Consortia (GCC).
