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.

Motivated candidates interested in pursuing postdoctoral research (recently awarded or submitted PhDs) are encouraged to contact the PI directly for applying to prestigious postdoctoral fellowship opportunities (such as the India Alliance DBT-Wellcome Trust Early Career Fellowship, DST-INSPIRE fellowship, SERB-NPDF, DBT-RA etc.) at least 3 months before the expected submission deadline. We also invite motivated students interested in pursuing doctoral research (leading to a PhD) or joining the lab as Integrated MSc-PhD students to write to the PI.

• Chandan Kumar
  Research Associate
  chandan@rcb.res.in
• Diksha Pathak
  PhD scholar (Senior Research Fellow)
  diksha.pathak@rcb.res.in
• Neeraj Wasnik
  PhD scholar (Senior Research Fellow)
  neeraj.wasnik@rcb.res.in
• Mahendra Singh
  PhD scholar (Senior Research Fellow)
  mahendra.singh@rcb.res.in
• Mahima
  PhD scholar (Senior Research Fellow)
  mahima.phd21@rcb.res.in
• Manya Batra
  PhD scholar (Junior Research Fellow)
  manya.batra@rcb.res.in
• Sukirti Khantwal
  PhD scholar (Junior Research Fellow)
  sukirti.khantwal@rcb.res.in
• Samadip Chowdhury
  PhD scholar (Junior Research Fellow)
  samadip.chowdhury@rcb.res.in
• Samanwita Ghosh
  PIntegrated MSc-PhD student
  samanwita.ghosh@rcb.res.in

Lab Alumni

• Harsh V Oza (former integrated MSc-PhD student)
  
• Anushka Das (former integrated MSc-PhD student)
  
• Dr. Sunayana Dagar (former PhD student)
  Current position: Postdoctoral fellow, Srinivasa Subramaniam Lab, UF Scripps Biomedical Research, Jupiter FL, USA.
  Formerly: postdoctoral fellow at Yale University, New Haven CT, USA
• Dr. Amrita Kumari (former PhD student)
  Current position: Postdoctoral fellow, Paul Kaufman Lab, University of Massachusetts Chan Medical School, Worcester MA, USA.
  
• Dr. Pushpa Kumari (India Alliance DBT-Wellcome Trust Early Career Fellow, 2014-2020)
  
• Monika Rawat (former integrated MSc-PhD student)
  
• Dr. Harsh Kumar (former PhD student) Current position: Postdoctoral fellow, Timothy McGraw Lab, Weill Cornell Medicine, New York NY, USA.
• Dr. Pergu Rajaiah (former PhD student)
  Current position: Postdoctoral fellow, Amit Choudhary Lab, Brigham and Women's Hospital, Harvard Medical School and the Broad Institute of MIT and Harvard, Cambridge USA.
• Dr. Amit Sharma (former PhD student)
  Current position: Postdoctoral fellow, Laurence Pelletier Lab, The Lunenfeld-Tanenbaum Research Institute and the University of Toronto, Toronto Canada.
• 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: Group leader/ staff scientist, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad Telangana, India.
  Formerly: Assistant Professor, Nirma University, Ahmedabad India.
  
• Dr. Megha Kumar (DST-INSPIRE faculty 2017-18; Young Investigator 2013-17)
  Current Position: Senior Scientist, CSIR Centre for Cellular and Molecular Biology, Hyderabad Telangana, India.
• Dr. Sharmishtha Samantaray (Young Investigator 2011-13)
  Current Position: Scientist III, Thermo Fisher Scientific, Bangalore India.

1. Saha S, Verma R, Kumar C, Kumar B, Dey A, Surjit M, Mylavarapu SVS, and Maiti TK* (2021). Proteomic analysis reveals USP7 as a novel regulator of palmitic acid-induced hepatocellular carcinoma cell death. Cell Death and Disease, Jun 22; 13(6):563. doi: 10.1038/s41419-022-05003-4.
2. Dagar S, Pathak D, Oza H and Mylavarapu SVS* (2021). Tunneling nanotubes and related structures: molecular mechanisms of formation and function. Biochem J, 478 (22): 3977-3998. doi: 10.1042/BCJ20210077
3. Kumari A, Kumar C, Pergu R, Mahale SP, Kumar M, and Mylavarapu SVS* (2021). Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions. Journal of Cell Biology, 220 (12): e202005184. doi:10.1083/jcb.20200518.
4. Srinivasan B, Samaddar S, Mylavarapu SVS, Clement JP and Banerjee S* (2021). Homeostatic scaling is driven by a translation-dependent degradation axis that recruits miRISC remodeling. PLoS Biology, https://doi.org/10.1371/journal.pbio.3001432.
5. Pushpa K*, Dagar S, Kumar H, Pathak D and Mylavarapu SVS* (2021). The exocyst complex regulates C. elegans germline stem cell proliferation by controlling membrane Notch levels. Development, 148 (15):dev196345. doi: 10.1242/dev.196345.
6. Kumari A, Kumar C, Wasnik N and Mylavarapu SVS* (2021). Dynein light intermediate chains as pivotal determinants of its multifunctionality. Journal of Cell Science, 134(10): jcs254870. Doi:10.1242/jcs.254870
7. Dagar S, Pushpa K, Pathak D, Samaddar S, Saxena A, Banerjee S and Mylavarapu SVS (2020) Nucleolin regulates 14-3-3ζ mRNA and promotes cofilin phosphorylation to induce tunneling nanotube formation. FASEB Journal, https://doi.org/10.1096/fj.202001152R.
8. Sharma A, Dagar S, Mylavarapu SVS (2020). Transgelin-2 and phosphoregulation of the LIC2 subunit of dynein regulate mitotic spindle orientation Journal of Cell Science, 133 (12):jcs239673. doi: 10.1242/jcs.239673. PMID: 32467330.
9. Ananthanarayanan V, Mylavarapu SVS (2020). Meeting report - the Microtubules, Motors, Transport and Trafficking (M2T2) 2019 meeting. Journal of Cell Science, 133 (8).
10. 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 132 (14). PMID 31221728.
11. 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.
12. 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.
13. 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.
14. Kumar M, Mylavarapu SV (2017) Role of Dynein Light Intermediate Chains in Embryonic divisions and Vertebrate Embryogenesis Mechanisms of Development 145:S62
15. 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
16. 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
17. Kumar M, Pushpa K, Mylavarapu SV (2015)  Splitting the cell, building the organism: Mechanisms of cell division in metazoan embryos IUBMB Life 67:575.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.