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Dr. Sivaram V S Mylavarapu

Associate Professor
E-mail: sivaram at rcb dot res dot in

  • PhD 2001, National Institute of Immunology
  • Postdoc at University of Massachusetts Medical School, USA
  • Associate Professor

Cell Division, Intercellular Communication and Cellular Dynamics

Our research group is interested in illuminating the fundamental molecular mechanisms regulating cell division and intercellular communication, with the aim to elucidate their impact on important biological processes. In the long term, we would like to exploit this detailed knowledge to design strategies for amelioration of disease conditions.

Mammalian cells divide with a high degree of fidelity, ensured through tight molecular regulation of multiple pathways, to generate two daughter cells that contain the correct diploid complement of chromosomes. Elucidation of the molecular mechanisms of mitotic regulation is imperative to understand the basis for asymmetric stem cell division leading to differentiation, for understanding early development of multicellular organisms, as well as for potential therapeutic intervention in major diseases such as cancer.

We are studying molecular events controlling the metaphase to anaphase cell cycle transition, monitored by the Spindle Assembly Checkpoint, and dissecting the role of the ubiquitous molecular motor, cytoplasmic dynein, in regulating multiple facets of this process. We are also exploring molecular control of cytokinesis, the terminal step of mitosis, to understand the role of both molecular motors and vesicular traffic in ensuring completion of cell division. Intricate knowledge of molecular mechanisms that control cell division could be exploited to design highly specific counter-measures to control cell division and consequently diseases like cancer.

Independently, we are probing the molecular basis for biogenesis and function of tunneling nanotubes - thin, tubular cytoplasmic connections between cells - a relatively novel mode of intercellular communication seen in several eukaryotes. These structures play important roles in various cellular processes underlying health and disease, such as in cancer metastasis and intercellular pathogen transmission. However the molecular mechanisms controlling their formation and function remain poorly understood. Knowledge of how these nano-conduits form and function, how they are hijacked by microbial pathogens for efficient intercellular transmission and how they are subverted for the benefit of cancerous cells could be used to design novel and specific therapeutic strategies.

Our approach to answering the above questions is multi-pronged. We employ cell biological studies, high-resolution and super-resolution optical microscopy including live cell imaging, biochemistry, proteomics, biophysical and structural biological approaches. We have extended our studies to two model organisms, the invertebrate Caenorhabditis elegans and the vertebrate zebrafish, to understand how these molecular mechanisms shape organism development.

We invite excellent and motivated recent PhDs in the life sciences to contact the PI directly for applying to prestigious postdoctoral fellowship opportunities. Students who have recently submitted their PhD thesis are also welcome. The lab has mentored competitive young postdoctoral fellows with similar/ complementary expertise as the lab, to enable them to progress to the next stage of their careers.

We invite excellent recent PhDs in the life sciences (students who have recently submitted their PhD thesis are also welcome) to contact the PI directly for applying to prestigious postdoctoral fellowship opportunities.

  • Pushpa Kumari
    Wellcome-DBT Early Career Fellow
    pushpa@rcb.res.in
  • Harsh Kumar
    Senior Research Fellow
    kharsh@rcb.res.in
  • Pergu Rajaiah
    Senior Research Fellow
    pergu@rcb.res.in
  • Amit Sharma
    Senior Research Fellow
    amit@rcb.res.in
  • Amrita Kumari
    Senior Research Fellow
    amrita.kumari@rcb.res.in
  • Sunayana Dagar
    Senior Research Fellow
    sunayana.dagar@rcb.res.in
  • Chandan Kumar
    Senior Research Fellow
    chandan@rcb.res.in

Lab Alumni
  • Dr. Sagar P Mahale (former PhD student)
    Current position: Postdoctoral fellow, Chandrasekhar Kanduri Lab, University of Gothenburg, Gothenburg Sweden.
  • Dr. Kuldeep Verma (former Young Investigator 2017-18)
    Current Position: Assistant Professor, Nirma University, Ahmedabad India.
  • Dr. Megha Kumar (DST-INSPIRE faculty 2017-18; Young Investigator 2013-17)
    Current Position: DST-INSPIRE Faculty at the CSIR Centre for Cellular and Molecular Biology, Hyderabad India.
  • Dr. Sharmishtha Samantaray (Young Investigator 2011-13)
    Current Position: Scientist III, Thermo Fisher Scientific, Bangalore India.
  1. Kumar H, Pushpa K, Kumari A, Verma K, Pergu R and Mylavarapu SVS (2019). The Exocyst complex and Rab5 are required for Abscission by Localizing ESCRT III Subunits to the Cytokinetic Bridge. Journal of Cell Science (provisionally accepted).
  2. Pergu R, Dagar S, Kumar H, Kumar R, Bhattacharya J and Mylavarapu SVS (2019). The chaperone ERp29 is required for tunnelling nanotube formation by stabilizing MSec. Journal of Biological Chemistry 294 (18): 7177-93.
  3. Dwivedi D, Kumari A, Rathi S, Mylavarapu SVS and Sharma M (2019). The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis. Journal of Cell Biology 218 (3): 871-894.
  4. Mylavarapu S, Kumar H, Kumar S, Sravanthi LS, Jain M, Basu A, Biswas M, Mylavarapu SVS, Das A and Roy M (2019). Activation of epithelial-mesenchymal transition and altered beta- catenin signalling in a novel Indian colorectal carcinoma cell line. Frontiers in Oncology 9: 54.
  5. Kumar M, Mylavarapu SV (2017) Role of Dynein Light Intermediate Chains in Embryonic divisions and Vertebrate Embryogenesis Mechanisms of Development 145:S62
  6. Mahale S, Kumar M, Sharma A, Babu A, Ranjan S, Sachidanandan C, Mylavarapu SV (2016) The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation.. Sci Rep 6:22
  7. Mahale S P, Sharma A, Mylavarapu SV (2016) Dynein Light Intermediate Chain 2 Facilitates the Metaphase to Anaphase Transition by Inactivating the Spindle Assembly Checkpoint. PLoS One 11:e0159646
  8. Kumar M, Pushpa K, Mylavarapu SV (2015)  Splitting the cell, building the organism: Mechanisms of cell division in metazoan embryos IUBMB Life 67:575.
  9. Sivaram MVS, Wadzinski TL, Redick SD, Manna T, Doxsey SJ. (2009) Dynein Light Intermediate Chain 1 is required for progress through the Spindle Assembly Checkpoint. EMBO J 28(7):902.
  10. Srijita Banerjee, Mirsamadi N, Anantharaman L, Sivaram MVS, Gupta RB, Choudhury D, Roy RP. (2007) Electrostatic modification of the axial contact residues impact sickle hemoglobin polymerization by perturbing a network of coupled interactions. Protein J 26 (7):445.
  11. Sivaram MVS, Furgason ML, Brewer DN, Munson M. (2006) The structure of the Exocyst subunit sec6p reveals a conserved architecture with diverse roles. Nature Structural and Molecular Biology 13(6):555.
  12. Sivaram MVS, Saporita JA, Furgason ML, Boettcher AJ, Munson M. (2005) Dimerization of the Exocyst protein Sec6 and its interaction with the t-SNARE Sec9. Biochemistry 44(16):6302.
  13. Sudha R, Anantharaman L, Sivaram MVS, Lohiya NK, Gupta RB, Roy RP. (2004) Linkage of interactions in sickle hemoglobin fiber assembly: inhibitory effect emanating from mutations in the AB region of the alpha-chain is annulled by a mutation at its EF corner. J Biol Chem 279 (19):20018.
  14. Sivaram MVS, Sudha R, Roy RP. (2001) A role for the alpha 113 (GH1) amino acid residue in the polymerization of sickle hemoglobin. J Biol Chem 276(21):18209.
  15. John MV, Parwez I, Sivaram MVS, Mehta S, Marwah N, Ali S. (1996) Analysis of VNTR loci in fish genomes using synthetic oligodeoxyribonucleotide probes. Gene 172:191.

Dr. Sivaram V S Mylavarapu
Associate Professor
Regional Centre for Biotechnology
NCR Biotech Science Cluster
3rd Milestone, Faridabad-Gurgaon Expressway
P.O. Box No. 3, Faridabad - 121 001
Haryana (NCR Delhi), India
E-mail: sivaram at rcb dot res dot in
Phone: 91 129-2848830

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