CSIR - Centre for Cellular & Molecular Biology
Council of Scientific and Industrial Research
Ministry of Science & Technology, Govt. of India
Emeritus Scientist
Email: vradha@ccmb.res.in
Phone: +91-040-27192619
Research Interests
Choice of a cell to undergo differentiation, division, or cell death forms the basis of development and functioning of tissues in multi-cellular organisms. Our interest has been in understanding the molecular players that regulate gene expression and cytoskeletal remodelling to guide cells to achieve specialized properties and form functional tissues. How these molecules respond to extracellular cues and simultaneously regulate multiple properties of the cell spatially and temporally has been our challenge. Salient findings have been, identification of the guanine nucleotide exchange factor, RapGEF1 as a regulator of actin dynamics, differentiation, and survival. RapGEF1 functions as a suppressor of ?-catenin and regulates chromatin dynamics. We have shown novel mechanisms of c-Abl and Bcr-Abl regulation, and our work has provided leads to understanding control of cell fate, and reversing the malignant phenotype of some human cancers. Ongoing work explores the molecular mechanisms involved in regulation of proliferation vs. differentiation in cells during development, and maintenance of homeostasis in adult tissues. Using cells in culture, we model physiological differentiation, and use human disease associated mutants to understand pathophysiology.
Selected Publications
Sanjeev Chavan Nayak, Vegesna Radha* (2020). C3G localizes to the mother centriole dependent on cenexin, and regulates centrosome duplication and primary cilia length. Journal of Cell Science 133(11) jcs.243113 doi: 10.1242/jcs.243113.
Raghawan A K, Rajashree R, Radha V*, and Swarup G*. (2019) HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4. Proc Natl Acad Sci, USA 116 (41), 20243-20244.
Dhruvkumar Shakyawar, Muralikrishna Bhattiprolu & Vegesna Radha* (2018) "C3G dynamically associates with nuclear speckles and regulates mRNA splicing". Mol Biol Cell 29(9):1111-1124.
Shakyawar DK, Dayma K, Ramadhas A, Varalakshmi C, Radha V*.(2017) C3G shows regulated nucleo-cytoplasmic exchange and represses histone modifications associated with euchromatin. Mol Biol Cell. 28: 984-995, 2017K.
Sasi Kumar, A. Ramadhas, S.C. Nayak, S. Kaniyappan, K. Dayma, V.Radha*(2015) C3G (RapGEF1), a regulator of actin dynamics promotes survival and myogenic differentiation of mouse mesenchymal cells. BBA-Mol. Cell Res. 1853: 2629-2639.
Education & Experience
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Title | Journal | Year |
---|---|---|
HSC70 as a sensor of low temperature: Role in cold-triggered autoinflammatory disorders | FEBS J | 2021 |
Complex formation and reciprocal regulation between GSK3beta and C3G. | Biochim Biophys Acta Mol Cell Res. | 2021 |
C3G Regulates STAT3, ERK, Adhesion Signaling, and Is Essential for Differentiation of Embryonic Stem Cells. | Stem Cell Rev and Rep | 2021 |
Consensus Scientific Statement on Advisory Working Guidelines and Recommendations for the Female Population in COVID-19 Era by WINCARS. | Indian J Cardiovascular Disease in Women | 2020 |
Understanding the SARS-CoV-2 to Manage COVID-19 | Indian J Cardiovascular Disease in Women | 2020 |
Expression of a novel brain specific isoform of C3G is regulated during development. | Sci Rep | 2020 |
The need to develop a framework for human-relevant research in India: Towards better disease models and drug discovery. | J Biosci | 2020 |
C3G localizes to the mother centriole in a cenexin-dependent manner, and regulates centrosome duplication and primary cilia length | J Cell Science | 2020 |
Expression of a novel brain specifc isoform of C3G is regulated during development. | Scientifc Reports | 2020 |
C3G localizes to the mother centriole in a cenexin-dependent manner, and regulates centrosome duplication and primary cilia length. | Journal of Cell Science jcs.243113 doi: 10.1242/jcs.243113. | 2020 |
HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4. | Proc Natl Acad Sci, USA | 2019 |
HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4. | Proc Natl Acad Sci, USA 116 (41), 20243-20244. | 2019 |
C3G dynamically associates with nuclear speckles and regulates mRNA splicing | Mol Biol Cell 29(9):1111-1124 PMID:29496966 | 2018 |
Development and characterization of a novel monoclonal antibody that recognizes an epitope in the central protein interaction domain of RapGEF1 (C3G). | Mol Biol Reports 2018 Aug 24. doi: 10.1007/s11033-018-4327-0. | 2018 |
A disease-associated mutant of NLRC4 shows enhanced interaction with SUG1 leading to constitutive FADD dependent caspase-8 activation and cell death. | J Biol Chem, 292(4):1218-1230. | 2017 |
C3G. Encyclopedia of Signaling Molecules | Springer Nature.Choi, Sangdun (Ed.) in Press.DOI 10.1007/978-1-4614-6438-9_101544- | 2017 |
CDC20siRNA and paclitaxel co-loaded nanometric liposomes of nipecotic acid-derived cationic amphiphile inhibit xenografted neuroblastoma. | Nanoscale; 9, 1201-1212. | 2017 |
C3G shows regulated nucleo-cytoplasmic exchange and represses histone modifications associated with euchromatin. | Mol Biol Cell. 28: 984-995, 2017 | 2017 |
661W is a retinal ganglionprecursor-like cell line in which glaucoma-associated optineurin mutants induce cell death selectively. | Scientific Reports, 4;7(1):16855 | 2017 |
pH and Thermo-sensitive 5 Fluorouracil loaded Poly (Nipam-co-AAc) Nanogels for Cancer Therapy. | RSC Advances; 6, 105495-105507 DOI: 10.1039/ C6RA18034E | 2016 |
Use of dominant negative/substrate trapping PTP mutations to search for PTP interactors /substrates. | Methods in Molecular Biology. 1447: 243-265. | 2016 |
C3G (RapGEF1), a regulator of actin dynamics promotes survival and myogenic differentiation of mouse mesenchymal cells. | BBA-Mol. Cell Res. Volume 1853, Issue 10, Part A, October 2015, Pages 2629-2639 | 2015 |
E50K-OPTN-induced retinal cell death involves the Rab GTPase-Activating Protein, TBC1D17 mediated block in autophagy. | PLoS One, 9(4): e95758 | 2014 |
M98K-optineurin induces transferrin receptor degradation and Rab12-mediated autophagic death in retinal ganglion cells. | Autophagy 9:510-527 | 2013 |
When a cell decides to die: multiple options. | Proc. AP Acad. Sci. 15: 41-46 | 2013 |
The tyrosine phosphatase TC48 interacts with and inactivates the oncogenic fusion protein BCR-Abl but not cellular Abl. | Biochim Biophys Acta. Mol.Basis of Dis. 1832: 275-284. | 2013 |
The tyrosine phosphatase TC48 interacts with and inactivates the oncogenic fusion protein BCR-Abl but not cellular Abl. | Biochim Biophys Acta. Mol.Basis of Dis. 1832: 275-284. | 2013 |
Dynamic changes in nuclear localization of a DNA-binding protein tyrosine phosphatase TCPTP in response to DNA damage and replication arrest. | Cell Biol Toxicol 28:409-419 | 2012 |
Reciprocal negative regulation between the guanine nucleotide exchange factor C3G and ?-catenin | Genes & Cancer 3:564-577 | 2012 |
The tyrosine phosphatase TC48 interacts with and inactivates the oncogenic fusion protein BCR-Abl but not cellular Abl. | Biochim Biophys Acta 1832 (1): 275-284 | 2012 |
Lamins, laminopathies and disease mechanisms: Possible role for proteasomal degradation of key regulatory proteins | J. Biosci., 36:471-479 | 2011 |
TC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and negatively regulates differentiation of human neuroblastoma cells. | PLoS ONE 6(8): e23681 | 2011 |
Cytoskeletal remodeling by C3G to induce neurite-like extensions and inhibit motility in highly invasive breast carcinoma cells. | BBA- Mol. Cell. Res. 1813: 456-465 | 2011 |
Signaling to actin: Role of C3G, a multitasking guanine nucleotide exchange factor. | Bioscience Reports 31: 231-244 | 2011 |
RAPGEF1 (Rap guanine nucleotide exchange factor (GEF) | Atlas Genet Cytogenet Oncol Haematol. | 2010 |
-actin binding domain of c-Abl regulates localized phosphorylation of C3G: Role of C3G in c-Abl mediated cell death . | Oncogene 29: 4528-4542 | 2010 |
Interaction with Sug1 enables Ipaf ubiquitination leading to caspase-8 activation and cell death. | Biochem. J. 427: 91-104. | 2010 |
Regulation of endocytic trafficking of transferrin receptor by optineurin and its impairment by a glaucoma-associated mutant. | BMC Cell Biol. 11: 4. | 2010 |
In vivo radioprotection by 5-aminosalicylic acid. | Mutation Research 650: 63-79. | 2008 |
The guanine nucleotide exchange factor, C3G regulates differentiation and survival of human neuroblastoma cells. | J. Neurochem. 107: 1424-1435. | 2008 |
CASPASE-1 | Atlas Genet Cytogenet. Oncol. Haematol. | 2007 |
IPAF / NLRC4 | Atlas Genet Cytogenet Oncol. Haematol. | 2007 |
Regulation of p73 by Hck through kinase-dependent and independent mechanisms. | BMC Molecular Biology 8: 45. | 2007 |
C3G is required for c-Abl induced filopodia and its overexpression promotes filopodia formation. | Exp. Cell Res. 313: 2476-2492. | 2007 |
A glaucoma associated mutant of optineurin selectively induces death of retinal ganglion cells which is inhibited by antioxidants. | IOVS 48: 1607-1614. | 2007 |
Involvement of caspase-1 and its activator Ipaf upstream of mitochondrial events in apoptosis. | FEBS J. 273: 2766-2778. | 2006 |
Role of p73 in regulating human caspase-1 gene transcription induced by Ifn-g & cisplatin. | J Biol. Chem.280: 36664-36673. | 2005 |
Transcriptional control of caspase gene expression. | PINSA 70:551-577. | 2004 |
Caspase-1 activator Ipaf is a p53 inducible gene involved in apoptosis. | Oncogene 24: 627-636. | 2004 |
Phosphorylated guanine nucleotide exchange factor C3G, induced by pervanadate and SFKs localizes to the Golgi and subcortical actin cytoskeleton. | BMC Cell Biol. 5: 31. | 2004 |
Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic activity | J. Biol. Chem. 278: 52188-52194. | 2003 |
A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1 dependent apoptosis. | Febs Letts. 532: 61-66. | 2002 |
Induction of cytochrome c release and apoptosis by Hck-SH3 domain- mediated signalling requires caspase-3. | Apoptosis 7: 195-207. | 2002 |
Direct transcriptional activation of human caspase-1 by tumor suppressor p53. | J. Biol. Chem. 276: 10585- 10588. | 2001 |
A nuclear protein tyrosine phosphatase induces shortening of G1 phase and increase in c-Myc protein level. | Exp. Cell Res. 265: 1-10. | 2001 |
Nuclear Matrix : Methods of Preparation. | Encyclopedia of Life Sciences p. 1-3 | 2001 |
PTP-S2, a nuclear tyrosine phosphatase is phosphorylated and excluded from condensed chromosomes during mitosis. | J. Biosci. 25: 33-40. | 2000 |
Induction of p53 dependent apoptosis upon overexpression of a nuclear PTPase. | FEBS Letts. 453: 308-312. | 1999 |
Nuclear protein tyrosine phosphatases and control of cell proliferation. | Curr. Sci. 73: 418-429. | 1997 |
Overexpression of a nuclear protein tyrosine phosphatase increases cell proliferation. | FEBS Letts. 409: 33-36. | 1997 |
Two splice variants of a tyrosine phosphatase differ in substrate specificity, DNA binding and subcellular location | J. Biol. Chem. 271: 26755- 26761. | 1996 |
Association of Lyn tyrosine kinase with the nuclear matrix and cell-cycle- dependent changes in matrix-associated tyrosine kinase activity. | Eur. J. Biochem. 236: 352-359. | 1996 |
Subcellular localization of a protein tyrosine phosphatase : Evidence for association with chromatin. | Biochemical J. 299: 41-47. | 1994 |
Stabilization of a protein tyrosine phosphatase mRNA upon mitogenic stimulation of T-lymphocytes | Biochim. Biophys. Acta. 1216: 205. | 1993 |
Binding of protein tyrosine phosphatase to DNA through the carboxy terminal non-catalytic domain. | Biochemistry 32: 2194. | 1993 |
Binding of protein tyrosine phosphatase to DNA through the carboxy terminal non-catalytic domain. | Biochemistry 32: 2194. | 1993 |
Protein tyrosine phosphatases as regulators of protein kinase activity. | Curr. Sci. 62: 462-469. | 1992 |
Identification of human disease genes based on their map position | Human Applied Genetics’ ed. Reddy, P.P. and Swarna, M. p. 104. | 1991 |
Genetic studies in higher animals : New strategies. | Curr. Sci. 60: 556. | 1991 |
Molecular cloning and expression of a protein tyrosine phosphatase showing homology with transcription factors Fos and Jun. | FEBS Letts. 280: 65. | 1991 |
Essential fatty acids and peptic ulcer disease. | GUT 27: 914. | 1987 |
Plasma lipoproteins and LCAT in chronic liver disease. | Ind. J. Gast. 6: 197. | 1987 |
Salivary IgA in peptic ulcer patients. | Curr. Sci. 56: 603. | 1987 |
The Genetics of Peptic Ulcer Disease. | Trop Gast. 6: 132. | 1985 |
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vradha@ccmb.res.in