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R. V. Omkumar, PhD

Scientist F

+91-471-2529483

omkumar@rgcb.res.in

omkumar
omkumar

R. V. Omkumar, PhD

Scientist F

+91-471-2529483

omkumar@rgcb.res.in

  • Profile

    • PhD Biochemistry – 1992 (Indian Institute of Science, Bangalore)
    • MSc Biochemistry – 1986 (University of Kerala, Thiruvananthapuram)
    • 2012: UGC Visiting Fellow, School of Life Sciences, Sree Ramanand Theerth Marathwada University, Nanded, Maharashtra, India
    • 2009: Visiting Scientist, Health Technology Research Centre, National Institute of Advanced Industrial Science and Technology (AIST), Japan
    • 2008 – Present: Scientist F, Rajiv Gandhi Centre for Biotechnology
    • 2004 – 2008: Scientist E-II, Rajiv Gandhi Centre for Biotechnology
    • 2000 – 2004: Scientist E-I, Rajiv Gandhi Centre for Biotechnology
    • 1996 – 2000: Scientist C, Rajiv Gandhi Centre for Biotechnology
    • 1994 – 1996: Post Doctoral Fellow, California Institute of Technology, Pasadena, USA
    • 1992 – 1994: Post Doctoral Fellow, Purdue University, West Lafayette, USA
    • Mrs. C. V. H. Rao Memorial Award for the Best Ph.D Thesis, Indian Institute of- -Science, Bangalore, India, 1992
    • Invention from the research group was selected among the top 50 innovations in all- -disciplines in india in 2012-13 by the DST-lockheed martin india innovation growth -programme (https://www.indiainnovates.in/)

    Membership in Professional Societies

    • Elected Fellow of the Kerala Academy of Sciences
    • Member representative from India in the School's Initiative of the International Society for-Neurochemistry, 2010-2013
    • Life Member of the Asia-Pacific Society for Neurochemistry
    • Member of the Society for Neurosciences, USA, 2013
    • Life Member of the Indian Academy of Neurosciences
    • Life Member of the Society for Neurochemistry, India
    • Life Member of the Society of Cell Biologists, India
    • Life Member of the Society of Biological Chemists, India
    • Life Member of the Society for Biotechnologists, India
    • Member, Society for Evolutionary and Integrative Biology

    Membership in Academic Bodies

    • Member, Board of Studies in Biochemistry, University of Kerala, india
    • Member, Board of Studies, School of Biosciences, Mahatma Gandhi University, Kottayam, India
    • Member, Doctoral Committee, SCMS Institute of Bioscience and Biotechnology Research and- -Development, Cochin, under Anna University, India
    • Member, Board of Studies in Neurosciences, Sree Chithra Thirunal Institute of Medical Sciences -Technology, Thiruvananthapuram, India
    1. Title of the Invention: “Assay for detection of transient intracellular Ca2+”.
      Inventors: Omkumar, R. V., Rajeevkumar, R., Mathew Steephan, Mayadevi, M. and Suma Priya, S.
      US Patent Granted: 8,304,198; Date of issue November – 06, 2012
    2. Title of the Invention: “Assay for detection of transient intracellular Ca2+”.
      Inventors: Omkumar, R. V., Rajeevkumar, R., Mathew Steephan, Mayadevi, M, Suma Priya, S., Arunkumar R., C. and Archana, G, M.
      US CIP Application No. : 13/661,787 (CIP) (PCT/IN08/000370); Date of Filing – October 26, 2012
    3. Title of the Invention: “Assay for detection of transient intracellular Ca2+”.
      Inventors: Omkumar, R. V., Rajeevkumar, R., Mathew Steephan, Mayadevi, M.,and Suma Priya, S.
      Europe application No. : 08 789 892.0
    4. Title of the Invention: “Assay for detection of transient intracellular Ca2+”.
      Inventors: Omkumar, R. V., Rajeevkumar, R., Mathew Steephan, Mayadevi, M.and Suma Priya, S.
      Indian application No.: 1276/CHE/2007 dated 06-06-2008
    5. Title of Invention : A process for the preparation of plant extract that can inhibit a neuronal ligand-gated calcium channel.
      Inventors: Omkumar, R. V. , Soumya Paul, and Mayadevi, M.
      Provisional Patent No.: 3616/CHE/2013, filed on 14-08-2013
  • Research

    Molecular Neurobiology

    The biochemical regulatory mechanisms occurring at junctions between neurons called synapses that underlie learning and memory as well as the pathology of neurodegenerative diseases are major subjects of interest of the Molecular Neurobiology group. Calcium signalling pathways in synapses play important roles in these conditions.
    One of the areas of focus is on the enzyme calcium /calmodulin dependent protein kinase II (CaMKII). Its interactions and their physiological relevance are being studied using techniques of enzyme kinetics, binding assays, imaging, etc. under in vitro conditions and also using techniques such as behavioural analysis of in vivo models.
    Another ongoing programme is on bioprospecting for neuropharmacological compounds by screening for calcium channel blockers and antiexcitoxic compounds. A novel method for calcium channel assays developed in the group is being used for this purpose

    Biochemical regulation at neuronal synapses

    Higher order brain functions such as learning and memory arise from fundamental biochemical events occurring in the nervous system. Signal transduction mediated by Ca2+ is involved in a variety of physiological events at neuronal synapses. The spatio-temporal variations in the magnitude of Ca2+ signals give rise to varied physiological responses ranging from long term potentiation (LTP) that underlie learning and memory to excitotoxicity that leads to neuronal death.
    Calcium/calmodulin dependent protein kinase II (CaMKII) plays an important role in decoding Ca2+signals. Our group is interested in understanding how the biochemical properties of CaMKII support cellular events such as synaptic plasticity. Towards this goal, we are investigating the structure-activity relationships and protein-protein interactions of CaMKII. Although the interaction of CaMKII with the N-methyl-D-aspartate (NMDA)-type glutamate receptor is known to occur in vivo,the structural details as well as the biochemical consequences of this interaction are still not completely understood. We have found that the binding of the GluN2B subunit of NMDA receptor modulates the function of CaMKII in a way that might support its role in synaptic plasticity. Currently we are focusing our efforts on identification of the amino acid residues of both the proteins that make mutual contacts using a combination of site-directed mutagenesis and binding assays under in vitro as well as under intracellular conditions. For expression of the proteins we use E. coli, Baculovirus/insect cell system and HEK-293 cells. The functional consequences of this interaction are also being investigated using binding assays and kinetic analysis of the activity of CaMKII. Experiments to validate the in vitro findings are being attempted using the primary neuronal culture system as well as the rat in vivo model. We are also searching for other proteins, which may be involved in binding interactions with CaMKII.
    NMDA receptor is regulated by phosphorylation. A site on GluN2B, Ser1303, is phosphorylated by CaMKII. We have found that this site is dephosphorylated by protein phosphatise 1 (PP1) present in the postsynaptic density (PSD). Currently we are investigating the physiological role of this phosphorylation.

    Bioprospecting for Neuroactive compounds

    Excitotoxicity is a cause of neuronal damage in many neuropathological conditions such as epilepsy, stroke, neurodegenerative diseases, etc. Excessive influx of calcium through channel proteins such as NMDA receptor into neurons leads to cell death. We are using an in vitro excitotoxicity model using primary neurons in culture to screen extracts from plants for their antagonistic effects on excitotoxicity. Since Ca2+-channel blockers could prevent excitotoxicity, we first screen plant extracts for the presence of blockers of Ca2+-channels such as NMDA receptor. For this purpose, we have developed a cell biological assay for Ca2+-channels. Extracts which show neuroprotective effect in vitro,are being tested for their efficacy in vivo using animal models of excitotoxicity.

  • Publications

    1. Cheriyan J, Mohanan A.G, Kurup P.K, Mayadevi M, and Omkumar R.V (2012) Effect of multimeric structure of CaMKII in the GluN2B-mediated modulation of kinetic parameters of ATP. PLoS One 7(9):e45064. doi: 10.1371/journal.pone.0045064.
    2. Mayadevi M, Sherin D.R, Keerthi V.S, Rajasekharan K.N, and Omkumar R.V (2012) Curcumin is an inhibitor of calcium/calmodulin dependent protein kinase II.Bioorg Med Chem. 20, p6040-6047.
    3. Prabhu Ramya R, Suma Priya S, Mayadevi M, and Omkumar R.V (2012) Regulation of phosphorylation at Ser(1303) of GluN2B receptor in the postsynaptic density.Neurochem Int. 61, p981-985.
    4. Cheriyan J, Kumar P, Mayadevi M, Surolia A, Omkumar R V (2011) Calcium/Calmodulin Dependent Protein Kinase II Bound to NMDA Receptor 2B Subunit Exhibits Increased ATP Affinity and Attenuated Dephosphorylation. PLoS ONE 6(3): e16495. doi:10.1371/journal.pone.0016495
    5. Biju V, Mundayoor S, Omkumar R.V, Anas A, and Ishikawa M. (2010) Bioconjugated quantum dots for cancer research: Present status, prospects and remaining issues. Biotechnol. Adv. 28, p199-213
    6. Muhammed M. A, Verma P.K, Pal S.K, Kumar R.C, Paul S, Omkumar R.V and Pradeep T. (2009) Bright, NIR-emitting Au23 from Au25: characterization and applications including biolabeling.Chemistry 15, p10110-20.
    7. Rajeevkumar R, Suma Priya S, Mayadevi M, Mathew Steephan, Santhoshkumar T.R, John Cheriyan, Sanalkumar R, Pradeep K.K, Jackson James, and Omkumar R.V . (2009) Phosphorylation status of the NR2B subunit of NMDA receptor regulates its interaction with Calcium/calmodulin dependent protein kinase II. J. Neurochem., 110, p 92-105.
    8. Pradeep K.K, John Cheriyan, Suma Priya S, Rajeevkumar R, Mayadevi M, Praseeda M, and Omkumar R.V. (2009) Modulation of catalysis of CaMKII by NMDA receptor subunit 2B. Biochem. J., 419, p123-32.
    9. Anshup J, Sai Venkataraman, Chandramouli Subramaniam, R. Rajeev Kumar, Suma Priya, T. R. Santhosh Kumar, R. V. Omkumar, Annie John and T. Pradeep (2005) Growth of Gold Nanoparticles in Human Cells. Langmuir 21, p 11562-7
    10. M. Praseeda, K.K. Pradeep, A. Krupa, S. Sri Krishna, S. Leena, R. Rajeev Kumar, John Cheriyan, M. Mayadevi, N. Srinivasan, and R. V. Omkumar (2004) Influence of a mutation in the ATP-binding domain of Calcium/Calmodulin dependent protein kinase II on its interaction with peptide substrates. Biochem. J. 378, p 391-397
    11. Praseeda M, Beena Mary K, Asha Sarah John, and Omkumar R.V. (2004) The C-terminus of CaMKII is truncated when expressed in E.coli. Protein Pept. Lett. 11, p 175-179
    12. Praseeda M, Mayadevi M, and Omkumar R.V. (2004) Interaction of Peptide substrate outside the active site influences catalysis by CaMKII. Biochem.Biophys.Res.Commun. 313, p 845-849
    13. Seetha, K, Banerjee, N. S, Omkumar R. V. and Purushothama, M. G. (2004) Cloning and Characterization of Partial Promoter of HMGCoA Reductase from Andrographis paniculata (Burm.f.) Wall.ex Nees – A Tropical medicinal Plant. J. Plant Biochem. Biotech. 14, p 41-44
    14. Mayadevi M, Praseeda M, Kumar K.S and Omkumar R.V. (2002) Sequence determinants on the NR2A and NR2B subunits of NMDA receptor responsible for specificity of phosphorylation by CaMKII. Biochem. Biophys. Acta. 1598, p 40-45.
    15. Omkumar R.V, Kiely M. J, Rosenstein A.J, Min K-T, and Kennedy M.B. (1996) Identification of a Phosphorylation Site for Calcium/Calmodulin-dependent Protein Kinase II in the NR2B Subunit of the N-Methyl-D-aspartate Receptor. J. Biol. Chem. 271, p 31670 – 31678
    16. Omkumar R. V and Rodwell V.W. (1994) Phosphorylation of Ser871 Impairs the Function of His865 of Syrian Hamster 3-Hydroxy-3-methylglutaryl-CoA Reductase. J. Biol. Chem. 269, p 16862 – 16866
    17. Omkumar R.V, Darnay B.G and Rodwell V.W. (1994) Modulation of Syrian Hamster 3-Hydroxy-3-methylglutaryl-CoA Reductase Activity by Phosphorylation. Role of Serine 871. J. Biol. Chem. 269 , p 6810 – 6814
    18. Omkumar R.V, Kadam S.M, Banerji A and Ramasarma T. (1993) On the Involvement of Intramolecular Protein Disulfide in the Irreversible Inactivation of 3-Hydroxy-3-methylglutaryl-CoA Reductase by Diallyl Disulfide. Biochim. Biophys. Acta 1164, p 108-112
    19. Omkumar R.V and Ramasarma T. (1993) Irreversible Inactivation of 3-Hydroxy-3-methylglutaryl-CoA Reductase by H2O2. Biochim. Biophys. Acta 1156, p 267-274
    20. Omkumar R.V, Gaikwad A.S, and Ramasarma T. (1992) Feedback-type Inhibition of Activity of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase by Ubiquinone. Biochim. Biophys. Res. Commun. 184, p 1280-1287
    21. Omkumar R.V, Mehta P.P, Ramakrishna Kurup C.K, and Ramasarma T. (1992) Preparation of a Soluble 58 kDa-3-hydroxy-3-methylglutaryl CoA Reductase from Liver Microsomes and its Inhibition by Ethoxysilatrane, a Hypocholesterolemic Compound. Mol. Cell. Biochem. 110, p 145-153
    22. Omkumar R.V, Banerji A, Kurup C.K.R and Ramasarma T. (1991) The Nature of Inhibition of 3-Hydroxy-3-methylglutaryl CoA Reductase by Garlic-derived Diallyl Disulfide. Biochim. Biophys. Acta 1078, p 219-225
    23. Ushadevi S, Omkumar R.V and Ramasarma T. (1988) Studies on the Distribution and Changes in Concentration of Iron and Iron-dependent Inhibitor Protein of Hydroxymethyl glutaryl CoA Reductase. Indian J. Biochem. Biophys. 25, p 664-673
  • Team


    Dr. Mathew John, Post Doctoral Fellow

    Synaptic calcium signalling initiated by NMDA receptor and voltage gated calcium channel activates CaMKII. My research aims to understand the signalling events downstream of CaMKII in cell models and in the in vivo rat model.

    mathew
    mathew

    Dr. Mathew John, Post Doctoral Fellow

    Synaptic calcium signalling initiated by NMDA receptor and voltage gated calcium channel activates CaMKII. My research aims to understand the signalling events downstream of CaMKII in cell models and in the in vivo rat model.

    Archana G M, PhD student

    Calcium/calmodulin dependent protein kinase II (CaMKII) is a key molecule involved in the process of learning and memory. A non-catalytic site on CaMKII called T-site mediates interaction with other proteins. Regulation of catalytic activity of CaMKII by T-site mediated interactions is my area of interest.

    archana
    archana

    Archana G M, PhD student

    Calcium/calmodulin dependent protein kinase II (CaMKII) is a key molecule involved in the process of learning and memory. A non-catalytic site on CaMKII called T-site mediates interaction with other proteins. Regulation of catalytic activity of CaMKII by T-site mediated interactions is my area of interest.

    Arunkumar R C, PhD Student

    I aim to develop an assay system to screen for calcium channel modulators, in a heterologous expression system based on the well characterized CaMKII-NR2B interaction.

    arun1
    arun1

    Arunkumar R C, PhD Student

    I aim to develop an assay system to screen for calcium channel modulators, in a heterologous expression system based on the well characterized CaMKII-NR2B interaction.

    Ramya Prabhu, PhD Student

    Phosphorylation/dephosphorylation of synaptic proteins play an important role in synaptic plasticity. I would like to study the phosphatases which are involved in regulating NMDA receptors and their physiological significance.

    remya
    remya

    Ramya Prabhu, PhD Student

    Phosphorylation/dephosphorylation of synaptic proteins play an important role in synaptic plasticity. I would like to study the phosphatases which are involved in regulating NMDA receptors and their physiological significance.

    Mantosh Kumar, PhD Student

    Excitotoxicity is one of the major causes for neuronal death which can occur by excessive activation of neuronal NMDA receptor. Compounds which could block NMDA receptor have therapeutic potential as neuroprotectants in conditions involving excitotoxicity. My aim is to establish and validate the neuroprotective effect of selected plant extracts and to identify the active principles in them using various assays at the cellular level and behavioural level.

    mantosh
    mantosh

    Mantosh Kumar, PhD Student

    Excitotoxicity is one of the major causes for neuronal death which can occur by excessive activation of neuronal NMDA receptor. Compounds which could block NMDA receptor have therapeutic potential as neuroprotectants in conditions involving excitotoxicity. My aim is to establish and validate the neuroprotective effect of selected plant extracts and to identify the active principles in them using various assays at the cellular level and behavioural level.

    Lakshmi K, PhD Student

    Binding of GluN2B subunit of NMDA receptor to CaMKII is known to modulate its catalytic activity. I will be studying the physiological implications of this catalytic modulation of CaMKII in synaptic plasticity and excitotoxicity.

    lakshmi1
    lakshmi1

    Lakshmi K, PhD Student

    Binding of GluN2B subunit of NMDA receptor to CaMKII is known to modulate its catalytic activity. I will be studying the physiological implications of this catalytic modulation of CaMKII in synaptic plasticity and excitotoxicity.

  • Alumni