Professional Education


  • Master of Science, Vellore Institute Technology (2012)
  • Bachelor of Science, University Of Madras (2009)
  • Doctor of Philosophy, Sungkyunkwan University (2019)

Stanford Advisors


All Publications


  • The effect of hairpin loop on the structure and gene expression activity of the long-loop G-quadruplex NUCLEIC ACIDS RESEARCH Ravichandran, S., Razzaq, M., Parveen, N., Ghosh, A., Kim, K. 2021; 49 (18): 10689-10706

    Abstract

    G-quadruplex (G4), a four-stranded DNA or RNA structure containing stacks of guanine tetrads, plays regulatory roles in many cellular functions. So far, conventional G4s containing loops of 1-7 nucleotides have been widely studied. Increasing experimental evidence suggests that unconventional G4s, such as G4s containing long loops (long-loop G4s), play a regulatory role in the genome by forming a stable structure. Other secondary structures such as hairpins in the loop might thus contribute to the stability of long-loop G4s. Therefore, investigation of the effect of the hairpin-loops on the structure and function of G4s is required. In this study, we performed a systematic biochemical investigation of model G4s containing long loops with various sizes and structures. We found that the long-loop G4s are less stable than conventional G4s, but their stability increased when the loop forms a hairpin (hairpin-G4). We also verified the biological significance of hairpin-G4s by showing that hairpin-G4s present in the genome also form stable G4s and regulate gene expression as confirmed by in cellulo reporter assays. This study contributes to expanding the scope and diversity of G4s, thus facilitating future studies on the role of G4s in the human genome.

    View details for DOI 10.1093/nar/gkab739

    View details for Web of Science ID 000715870700038

    View details for PubMedID 34450640

    View details for PubMedCentralID PMC8501965

  • Unraveling the Regulatory G-Quadruplex Puzzle: Lessons From Genome and Transcriptome-Wide Studies FRONTIERS IN GENETICS Ravichandran, S., Ahn, J., Kim, K. 2019; 10: 1002

    Abstract

    G-quadruplexes (G4s) are among the best-characterized DNA secondary structures and are enriched in regulatory regions, especially promoters, of several prokaryote and eukaryote genomes, indicating a possible role in cis regulation of genes. Many studies have focused on evaluating the impact of specific G4-forming sequences in the promoter regions of genes. However, the lack of correlation between the presence of G4s and the functional impact on cis gene regulation, evidenced by the variable expression fold change in the presence of G4 stabilizers, shows that not all G4s affect transcription in the same manner. This indicates that the regulatory effect of the G4 is significantly influenced by its position, the surrounding DNA topology, and other environmental factors within the cell. In this review, we compare individual gene studies with high-throughput differential expression studies to highlight the importance of formulating a combined approach that can be applied in humans, bacteria, and viruses to better understand the effect of G4-mediated gene regulation.

    View details for DOI 10.3389/fgene.2019.01002

    View details for Web of Science ID 000494338000001

    View details for PubMedID 31681431

    View details for PubMedCentralID PMC6813735

  • Pneumococcal VncR Strain-Specifically Regulates Capsule Polysaccharide Synthesis FRONTIERS IN MICROBIOLOGY Ghosh, P., Shah, M., Ravichandran, S., Park, S., Iqbal, H., Choi, S., Kim, K., Rhee, D. 2019; 10: 2279

    Abstract

    Capsular polysaccharides (CPS), a major virulence factor in Streptococcus pneumoniae, become thicker during blood invasion while not during asymptomatic nasopharyngeal colonization. However, the underlying mechanism controlling this differential pneumococcal CPS regulation remain unclear. Here, we show how VncR, the response regulator of the vancomycin resistance locus (vncRS operon), regulates CPS expression in vncR mutants in three serotype (type 2, 3, and 6B) backgrounds upon exposure to serum lactoferrin (LF). Comparative analysis of CPS levels in the wild type (WT) of three strains and their isogenic vncR mutants after LF exposure revealed a strain-specific alteration in CPS production. Consistently, VncR-mediated strain-specific CPS production is correlated with pneumococcal virulence, in vivo. Electrophoretic mobility-shift assay and co-immunoprecipitation revealed an interaction between VncR and the cps promoter (cpsp) in the presence of serum. In addition, in silico analysis uncovered this protein-DNA interaction, suggesting that VncR binds with the cpsp, and recognizes the strain-specific significance of the tandem repeats in cpsp. Taken together, the interaction of VncR and cpsp after serum exposure plays an essential role in regulating differential strain-specific CPS production, which subsequently determines strain-specific systemic virulence. This study highlights how host protein LF contributes to pneumococcal VncR-mediated CPS production. As CPS plays a significant role in immune evasion, these findings suggest that drugs designed to interrupt the VncR-mediated CPS production could help to combat pneumococcal infections.

    View details for DOI 10.3389/fmicb.2019.02279

    View details for Web of Science ID 000491276300001

    View details for PubMedID 31632380

    View details for PubMedCentralID PMC6781885

  • Z-DNA in the genome: from structure to disease. Biophysical reviews Ravichandran, S., Subramani, V. K., Kim, K. K. 2019; 11 (3): 383-387

    Abstract

    The scope of studies investigating the architecture of genomic DNA has progressed steadily since the elucidation of the structure of B-DNA. In recent years, several non-canonical DNA structures including Z-DNA, G-quadruplexes, H-DNA, cruciform DNA, and i-motifs have been reported to form in genomic DNA and are closely related to the evolution and development of disease. The ability of these structures to form in genomic DNA indicates that they might have important cellular roles and are therefore retained during evolution. Understanding the impact of the formation of these secondary structures on cellular processes can enable identification of new targets for therapeutics. In this review, we report the state of understanding of Z-DNA structure and formation and their implication in disease. Finally, we state our perspective on the potential of Z-DNA as a therapeutic target.

    View details for DOI 10.1007/s12551-019-00534-1

    View details for PubMedID 31119604

  • Chemical-induced formation of BZ-junction with base extrusion BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Subramani, V., Ravichandran, S., Bansal, V., Kim, K. 2019; 508 (4): 1215-1220

    Abstract

    The crystal structure of BZ-junction reveals that left-handed Z-DNA stabilized by Z-DNA binding domain (Zα) is continuously stacked to right-handed B-DNA with AT bases' extrusion in the junction site. However, this structure might not fully represent the BZ-junction in solution due to the possibility of the junction formation either by crystal packing or Zα interaction. Therefore, we investigated BZ-junction in solution with chemical Z-DNA inducers using CD and 2-aminopurine base-extrusion assay. We confirmed the formation of Z-DNA and BZ-junction with base-extrusion by chemical Z-DNA inducers. However, neither typical Z-DNA nor base-extrusion could be detected with some inducers such as spermine, suggesting that the energy barrier for the formation of the BZ junction might vary depending on the Z-DNA induction conditions.

    View details for DOI 10.1016/j.bbrc.2018.12.045

    View details for Web of Science ID 000456491900036

    View details for PubMedID 30558789

  • Genome-wide analysis of regulatory G-quadruplexes affecting gene expression in human cytomegalovirus PLOS PATHOGENS Ravichandran, S., Kim, Y., Bansal, V., Ghosh, A., Hur, J., Subramani, V., Pradhan, S., Lee, M., Kim, K., Ahn, J. 2018; 14 (9): e1007334

    Abstract

    G-quadruplex (G4), formed by repetitive guanosine-rich sequences, is known to play various key regulatory roles in cells. Herpesviruses containing a large double-stranded DNA genome show relatively higher density of G4-forming sequences in their genomes compared to human and mouse. However, it remains poorly understood whether all of these sequences form G4 and how they play a role in the virus life cycle. In this study, we performed genome-wide analyses of G4s present in the putative promoter or gene regulatory regions of a 235-kb human cytomegalovirus (HCMV) genome and investigated their roles in viral gene expression. We evaluated 36 putative G4-forming sequences associated with 20 genes for their ability to form G4 and for the stability of G4s in the presence or absence of G4-stabilizing ligands, by circular dichroism and melting temperature analyses. Most identified sequences formed a stable G4; 28 sequences formed parallel G4s, one formed an antiparallel G4, and four showed mixed conformations. However, when we assessed the effect of G4 on viral promoters by cloning the 20 putative viral promoter regions containing 36 G4-forming sequences into the luciferase reporter and monitoring the expression of luciferase reporter gene in the presence of G4-stabilizing chemicals, we found that only 9 genes were affected by G4 formation. These results revealed promoter context-dependent gene suppression by G4 formation. Mutational analysis of two potential regulatory G4s also demonstrated gene suppression by the sequence-specific G4 formation. Furthermore, the analysis of a mutant virus incapable of G4 formation in the UL35 promoter confirmed promoter regulation by G4 in the context of virus infection. Our analyses provide a platform for assessing G4 functions at the genomic level and demonstrate the properties of the HCMV G4s and their regulatory roles in viral gene expression.

    View details for DOI 10.1371/journal.ppat.1007334

    View details for Web of Science ID 000448975900039

    View details for PubMedID 30265731

    View details for PubMedCentralID PMC6179306

  • Bioinorganic Nanohybrid Catalyst for Multistep Synthesis of Acetaminophen, an Analgesic ACS APPLIED MATERIALS & INTERFACES San, B., Ravichandran, S., Park, K., Subramani, V., Kim, K. 2016; 8 (44): 30058-30065

    Abstract

    A bioinorganic nanohybrid catalyst was synthesized by combining esterase with a platinum nanoparticle (PtNP). The combination of two catalysts resulted in enhanced catalytic activities, esterase hydrolysis, and hydrogenation in PtNPs, as compared to each catalyst alone. This hybrid catalyst can be successfully used in the multistep synthesis of acetaminophen (paracetamol), an analgesic and antipyretic drug, in a one-pot reaction with high yield and efficacy within a short time, demonstrating that the nanobiohybrid catalyst offers advantages in the synthesis of fine chemicals in industrial applications.

    View details for DOI 10.1021/acsami.6b12875

    View details for Web of Science ID 000387737200025

    View details for PubMedID 27797174

  • A novel approach for the biosynthesis of silver oxide nanoparticles using aqueous leaf extract of Callistemon lanceolatus (Myrtaceae) and their therapeutic potential JOURNAL OF EXPERIMENTAL NANOSCIENCE Ravichandran, S., Paluri, V., Kumar, G., Loganathan, K., Venkata, B. 2016; 11 (6): 445-458