preloader

Faculty

Arumugam Rajavelu

Arumugam Rajavelu

Ph. D.,Jacobs University Bremen, Germany,

M. Sc., University of Madras, Chennai

Assistant Professor

arumugam.rajavelu@iitm.ac.in

Office : BT 202 Block -1

+91-44-2257-4144

Academic positions

  • Assistant Professor: July 2021 - till date, Dept of Biotechnology, Indian Institute of Technology, Chennai, Tamil Nadu, India.

  • Program Scientist: Dec 2018 - June 2021, Rajiv Gandhi Center for Biotechnology (RGCB), Trivandrum, Kerala, India.

  • DST-INSPIRE faculty: Dec 2013 - Nov 2018, Rajiv Gandhi Center for Biotechnology (RGCB), Trivandrum, Kerala, India.

  • Post doctoral fellow: Dec 2011 - Nov 2013, Institute of Biochemistry, Stuttgart University, Stuttgart, Germany.

  • Junior Research fellow: Dec 2005 - June 2008, Department of Biochemistry, Indian Institute of Science (IISc), Bangalore, India.

Awards and Fellowships

  • Young Scientist Medal (2019), from Indian Society for Parasitology, JNU, New Delhi.

  • Kerala State Young Scientist award (2019), KSCSTE, Govt of Kerala.

  • SERB Early Career award (2016), Department of Science & Technology, Govt of India.

  • DBT - IYBA award (2015), Department of Biotechnology, Govt of India.

  • DST-INSPIRE faculty award (Aug 2013), Department of Science and Technology, Govt of India.

  • Postdoctoral Fellowship from Stuttgart University, funded by German Research Foundation (DFG), Stuttgart, Germany

  • PhD Fellowship funded by German Research Foundation (DFG), Germany (July 2008 - Sep 2011). PhD awarded with Special Distinction.

  • DBT JRF fellowship from Indian Institute of Science (IISc), funded by Dept of Biotechnology, Govt of India.

Research interest: Molecular Epigenetics & Plasmodium Biology

Epigenetic mechanisms of malaria parasite-host cell interactions

Research work in our laboratory is focused on Infection Biology; we aim to study the host-pathogen interactions through exploring the various Epigenetic signals of human malaria-causing pathogen and host. The obligate intracellular pathogens utilize the host factors for its growth and to establish chronic infections. Thus, it is highly essential to understand the molecular regulators of pathogens and the host cells that are involved in these processes and further it will be exploited to design better treatment strategies against infectious diseases. Using various Biochemical and Cell biology tools and genetic knockout strategies, we aim to study these processes in two important human pathogens viz Plasmodium spp. and Toxoplasma spp. We reported functions tRNA-specific methyltransferase from P. falciparum (BBA-Gene Regulatory Mechanisms, 2017) and characterized m6A RNA methyl-specific reader protein from P. falciparum (Epigenetics & Chromatin, 2020). Further, we have identified a novel epigenetic mechanism that controls the exported family surface proteins and virulence mechanisms in the malaria parasite that mediate the development of severe forms of cerebral malaria in humans (J Biol Chem, 2021); (ChemBioChem, 2018). Overall, our lab aims to understand the host-pathogen interactions for better drug and vaccine design against infectious diseases such as Malaria and Toxoplasmosis.

Project 1: Epigenetic control of virulence proteins expression in Plasmodium spp.

The P. falciparum expresses and exports highly variable proteins on the surface of infected RBC for cytoadherence. The parasite changes its variable protein in response to host immunity. The variable proteins are encoded by multigene family (~60 genes), and located at the subtelomeric regions across all 14 chromosomes. It expresses one var gene at the time of infection and maintains the remaining 59 var genes in suppressed state. The gene suppressor mechanism is achieved through clustering of var genes to nuclear periphery. It has been shown that H3K36me3 is highly enriched in repressor clusters, however the mechanisms in which the H3K36me3 methyl mark is propagated, and forms suppressor var gene clusters to nuclear periphery is unknown. We have identified PHD domain that binds strongly to methyl mark and allosterically stimulates the enzyme activity to propagate H3K36me3 methyl marks and clusters var genes into nuclear periphery. Our preliminary study has identified novel mechanisms of var genes expression in Plasmodium spp (Figure 1) and detailed study on this line would pave way for better vaccine designs against malaria.

Project 2: Molecular basis of Exportome regulation in Plasmodium spp to remodel the iRBCs

We have identified epigenetic methyl marks at unconventional sites on core histones of P. falciparum. Interestingly, all these methylations sites are located at the core histone on lateral surface of the nucleosome and reside very proximal to DNA contact point on histones. We characterized H3K64me3 mark and found it highly dynamic on the chromatin, enriched in ring, trophozoite stages and reduced in multinucleated schizont stage. This is first evidence show the dynamic deposition of the histone methylation marks in various developmental stages of P. falciparum. We have done a detailed characterization of H3K64me3 mark and have identified that the PfSET4 and PfSET5 enzymes of P. falciparum specifically methylate at H3K64. The global ChIP sequencing analysis has revealed that stage-specific dynamic distribution of H3K64me3 regulates the exportome family proteins in Plasmodium spp. This is first molecular evidence that shows the direct role of epigenetic players in stage specific gene expressions (J Biol Chem, 2021).

Project 3: Understanding the mechanisms of artemisinin drug resistant P. falciparum

The artemisinin drug resistant P. falciparum is emerging problem to the tropical countries. Recent reports identified that the parasite harbors mutations in ubiquitin ligase adaptor Kelch13 protein in propeller domain. We hypothesized that K13 protein mutations could bring the differential proteome of metabolic pathways associated proteins in P. falciparum to exert the resistant to artemisinin. The preliminary data from our lab identified that selective -gain and loss- of proteins in artemisinin resistant parasites. The MALDI analyses have identified three important proteins that are associated with metabolic activity shows differential expression in artemisinin resistant P. falciparum. Further characterization of these proteins would identify the mechanisms of drug resistance and will find path for drug discovery against resistant malaria parasite.

Research publications

2021

  1. Devadathan VS, CA Jabeena, Govindaraju G, Aparna S, Rajavelu A*. The severity of SARS-CoV-2 infection is dictated by host factors? Epigenetic perspectives. Current Research in Microbial Sciences, 2021, in press.

  2. Gayathri G, Chavali S, Rajavelu A*. Plasmodium falciparum YTH2 domain binds to m6A containing mRNA and regulates translation. mBio. 2021, in press.

  3. Mukesh RK, Kalam AA, Nag J, Jaikumar VS, Kunnakkadan U, Suma NM, Rajavelu A, Johnson JB. Chandipura virus induces cell death in cancer cell lines of human origin and promotes tumor regression in vivo. Molecular Therapy – Oncolytics, 2021, Dec 17; Vol 23; 254 -265.

  4. Devadathan VS, Govindaraju G, CA Jabeena, Rajavelu A*. The SET2 domain is allosterically regulated by its PHD domain to methylate at H3K36 in Plasmodium falciparum. BBA Gene Regulatory Mechanisms, 2021 oct; 1865(10): 194744.

  5. Khan MIK, Charles RCM, Ramachandran R, Gupta S, Govindaraju G, Mishra R, Rajavelu A, Coumar MS, Chavali S, Dhayalan A. The ribosomal protein eL21 interacts with the protein lysine methyltransferase SMYD2 and regulates its steady state levels. Biochim Biophys Acta Mol Cell Res. 2021 Aug;1868(9):119079.

  6. Jabeena CA, Govindaraju G, Devadathan VS, Soundararajan G, Jaleel A, Dhakshmi S, Rajavelu A*. Dynamic association of the H3K64 trimethylation mark on the genes encoding exported proteins in Plasmodium falciparum. J Biol Chem. 2021 Apr 8; 296:100614.

  7. Thomas JM, Surendran S, Abraham M, Rajavelu A*, Kartha CC*. Aberrant regulation of retinoic acid signaling genes in cerebral Arterio Venous Malformation nidus and neighbouring astrocytes. Journal of Neuroinflammation. 2021, Mar 1; 18(1): 61. *Corresponding authors.

  8. Verma M, Khan MI, Chakrapani B, Awasthi S, Mahesh A, Govindaraju G, Chavali PL, Rajavelu A, Chavali S, Dhayalan A. PRMT3 interacts with ALDH1A1 and regulates gene expression by inhibiting retinoic acid. Communications Biology, 2021 Jan 25; 4 (1): 109.

2020

  1. Chakrapani B, Khan MI, Verma M, Awasthi S, Govindaraju G, Mahesh A, Rajavelu A, Chavali S, Dhayalan A. The uncharacterized protein FAM47E interacts with PRMT5 and regulates its functions. Life Science Alliance, 2020 Dec 29; 4(3): e202000699.

  2. Govindaraju G, Varma RSK, Jabeena CA, Devadathan VS, Chavali S, Rajavelu A*. N6-Adenosine methylation, a regulatory mark on mRNA is recognized by YTH domain protein in human malaria parasite P. falciparum. Epigenetics & Chromatin, 2020, 13 (1), 33.

  3. Mahesh A, Khan MI, Govindaraju G, Verma M, Awasthi S, Chavali PL, Chavali S, Rajavelu A*, Dhayalan A*. SET7/9 interacts and methylates the ribosomal protein, eL42 and regulates protein synthesis. BBA – Molecular Cell Research. 2020 Feb;1867(2):118611. *Corresponding authors.

2019

  1. Jabeena CA, Rajavelu A*. Epigenetic players of chromatin structure regulation in Plasmodium falciparum. ChemBioChem. 2019 , 15, 20(10).

2018

  1. Awasthi S, Verma M, Mahes A, Khan MI, Govindaraju G, Rajavelu A, Chaval PL, Chavali S, Dhayalan A. DDX49 is an RNA helicase that affects translation by regulating mRNA export and the levels of pre-ribosomal RNA. Nucl Acid Res. 2018, Mar 30. 46(12):6304-6317.

  2. Rajavelu A, Lungu C, Emperle M, Dukatz M, Bröhm A, Broche J, Hanelt I, Parsa E, Schiffers S, Karnik R, Meissner A, Carell T, Rathert P, Jurkowska RZ, Jeltsch A. Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2. Nucl Acid Res. 2018 Sep 28; 46 (17):9044-9056.

  3. Emperle M, Dukatz M, Kunert S, Holzer K, Rajavelu A, Jurkowska RZ, Jeltsch A. The DNMT3A R882H mutation does not cause dominant negative effects in purified mixed DNMT3A/R882H complexes. Sci Rep. 2018 Sep 5;8(1):13242.

  4. Emperle M, Rajavelu A, Kunert S, Arimondo PB, Reinhardt R, Jurkowska RZ, Jeltsch A. The DNMT3A R882H mutant displays altered flanking sequence preferences. Nucl Acid Res. 2018 Apr 6;46(6):3130-3139.

  5. Thomas JM, Surendran S, Abraham M, Rajavelu A*, Kartha CC*. Gene expression analysis of nidus of cerebral arteriovenous malformations reveals vascular structures with deficient differentiation. Plos One, 2018, 13; 13 (6). *Corresponding authors.

2017

  1. Govindaraju G, Jabeena CA, Sethumadhavan DV, Rajaram N, Rajavelu A*. DNA methyltransferase homologue TRDMT1 in Plasmodium falciparum specifically methylates endogenous aspartic acid tRNA. BBA – Gene Regulatory Mechanisms. 2017 Oct; 1860(10): 1047-1057.

  2. Verma M, Chandar R, Chakrapani B, Coumar MS, Govindaraju G, Rajavelu R, Chavali S, Dhayalan A. PRMT7 interacts with ASS1 and citrullinemia mutations disrupt the Interaction. J Mol Biol. 2017, 429 (15): 2278 – 2289.

2016

  1. Thomas JM, Surendran S, Abraham M, Rajavelu A*, Kartha CC*. Genetic and Epigenetic mechanisms in the development of arteriovenous malformation in the brain. Clinical Epigenetics. 2016, 8 (1), 78. *Corresponding authors.

From PhD & PDF work

  1. Deplus R#, Blanchon L#, Rajavelu A#, Boukaba H# et al (2014). Regulation of DNA methylation patterns by CK2 mediated phosphorylation of Dnmt3a. Cell Reports. 8 (3); 743-753. #Shared first authors

  2. Emperle M, Rajavelu A, Reinhardt R, Jurkowska R, Jeltsch A (2014). Cooperative DNA binding and protein/DNA fiber formation increases the activity of the Dnmt3a DNA methyltransferase. J Biol Chem. 289 (43), 29602-29613.

  3. Bashtrykov P, Rajavelu A, Hackner B, Ragozin S, Carell T, Jeltsch A (2014). Targeted mutagenesis results in an activation of DNA methyltransferase 1 and confirms an autoinhibitory role of its RFTS domain. ChemBioChem. 9(3), 743-8.

  4. Rilova E, Erdmann A, Gros C, Masson V, Aussagues, Cassabois VP, Rajavelu A, et al (2014). Design, Synthesis and Biological Evaluation of 4‐Amino‐N‐(4‐aminophenyl) benzamide Analogues of Quinoline‐Based SGI‐1027 as Inhibitors of DNA Methylation. ChemMedChem. 9 (3), 590-601.

  5. S Asgatay, C Champion, G Marloie, T Drujon, C Senamaud-Beaufort, Ceccaldi A, Erdmann A, Rajavelu A et al (2014). Synthesis and Evaluation of Analogues of N-Phthaloyl-L-tryptophan (RG108) as Inhibitors of DNA Methyltransferase 1. J Med Chem. 57 (2), 421-434.

  6. Ceccaldi A*, Rajavelu A*, Ragozin S, Senamaud-Beaufirt C, Bashtrykov P, Testa N, Dali-Ali H, Maulay-Bailly C, Amand S, Guianvarc’h D, Jeltsch A, Arimondo PB (2013). Identification of Novel Inhibitors of DNA methylation by Screening of a Chemical Library. ACS Chemical Biology. 8 (3); 543-8. *shared first authors

  7. Rajavelu A, Jurkowska R, Fritz J, Jeltsch A (2012). Function and disruption of DNA Methyltransferase 3a cooperative DNA binding and nucleoprotein filament formation. Nucleic Acid Res, 40(2): 569-80.

  8. Jurkowska R*, Rajavelu A* Anspach N, Urbanke C, Jankevicius G, Ragozin S, Nellen W, Jeltsch A (2011). Oligomerization and Binding of the Dnmt3a DNA Methyltransferase to Parallel DNA Molecules: Heterochromatic localization and role of Dnmt3L. J Biol Chem. 286 (27); 24200-7. *shared first authors

  9. Siddique AN*, Nunna S*, Rajavelu A, Zhang Y, Jurkowska RZ, Reinhardt R, Rots MG, Jurkowski T & Jeltsch A. Targeted methylation and gene silencing of VEGF-A in human cells by using a Dnmt3a-Dnmt3L single-chain fusion protein with increased DNA methylation activity. J Mol Biol. 425(3), 479-91. *shared first authors

  10. Rajavelu A, Tulyasheva Z, Jaiswal R, Jeltsch A*, Kuhnert N* (2011). The inhibition of the mammalian DNA methyltransferase 3a (Dnmt3a) by dietary black tea and coffee polyphenols. BMC Biochem. 12; 16.

  11. Halby L, Sénamaud-Beaufort C, Ajjan S, Ceccaldi A, Drujon T, Rajavelu A, Champion C, Jurkowska R, Lequin O, Nelson WG, Jeltsch A, Guy A, Guianvarc’h D, Ferroud C and Arimondo PB (2012). Rapid synthesis of new DNMT inhibitors derivatives of Procainamide. ChemBioChem, 13(1): 157-65.

  12. Ceccaldi A, Rajavelu A, Champion C, Rampon C, Jurkowska R, Jankevicius G, Sénamaud-Beaufort C, Ponger L, Gagey N, Dali Ali H, Tost J, Vriz S, Ros S,Dauzonne D, Jeltsch A, Guianvarc’h D, Arimondo PB (2011). C5-DNA methyltransferase Inhibitors: From Screening to Effects on Zebrafish Embryo Development. Chembiochem. 14; 12 (9); 1337-45.

  13. Dhayalan A, Rajavelu A, Rathert P, Tamas R, Jurkowska RZ, Ragozin S, Jeltsch A (2010). The Dnmt3a PWWP domain reads histone 3 lysine 36 trimethylation and guides DNA methylation. J Biol Chem. 285(34); 26114-20.

  14. Zhang Y, Jurkowska R, Soeroes S, Rajavelu A, Dhayalan A, Bock I, Rathert P, Brandt O, Reinhardt R, Fischle W, Jeltsch A (2010). Chromatin methylation activity of Dnmt3a and Dnmt3a/3L is guided by interaction of the ADD domain with the histone H3 tail. Nucleic Acids Res. 38(13); 4246-53.

  15. Nagaraj VA, Arumugam R, Prasad D, Rangarajan PN, Padmanaban G (2010). Protoporphyrinogen IX oxidase from Plasmodium falciparum is anaerobic and is localized to the mitochondrion. Mol Biochem Parasitol. 174(1):44-52.

  16. Nagaraj VA, Prasad D, Arumugam R, Rangarajan PN, Padmanaban G (2010). Characterization of coproporphyrinogen III oxidase in Plasmodium falciparum cytosol. Parasitol Int. 59(2):121-7.

  17. Nagaraj VA, Arumugam R, Chandra NR, Prasad D, Rangarajan PN, Padmanaban G (2009). Localisation of Plasmodium falciparum uroporphyrinogen III decarboxylase of the heme-biosynthetic pathway in the apicoplast and characterization of its catalytic properties. Int J Parasitol. 39(5):559-68.

  18. Nagaraj VA, Arumugam R, Gopalakrishnan B, Jyothsna YS, Rangarajan PN, Padmanaban G (2008). Unique properties of Plasmodium falciparum porphobilinogen deaminase. J Biol Chem. 283(1): 437-44.