Qualification: 
Ph.D, MSc, BSc
jyotsnanambiar@am.amrita.edu
Phone: 
+919567656948

Dr. Jyotsna Nambiar currently serves as an Assistant Professor at the School of Biotechnology, Amritapuri campus. She completed her Ph.D. in Biotechnology from the Amrita Vishwa Vidyapeetham in the year 2016. During her Ph.D., she was involved in understanding the regulation of Matrix metalloproteinases in cancer cells by several natural product extracts.

ALMA MATER

  • Ph.D. Biotechnology (2016)
  • MSc. Biotechnology, Amrita Vishwa Vidyapeetham (2009)
  • B.Tech. Biotechnology, Jawaharlal Nehru Technological University, Hyderabad (2007)

AWARDS / HONOR

  • Qualified CSIR-UGC Junior Research Fellowship, 2009

RESEARCH PROJECTS

  • Anacardic Acid – A novel template for cancer therapy
  • Elucidating the molecular mechanisms of Anacardic Acid mediated regulation of Matrix Metalloproteinases in Cancer

Publications

Publication Type: Journal Article

Year of Publication Publication Type Title

2016

Journal Article

Dr. Jyotsna Nambiar, Bose, C., Venugopal, M., Asoke Banerji, Patel, T. B., Geetha B Kumar, and Nair, B. G., “Anacardic acid inhibits gelatinases through the regulation of Spry2, MMP-14, EMMPRIN and RECK.”, Exp Cell Res, vol. 349, no. 1, pp. 139-151, 2016.[Abstract]


Earlier studies from our laboratory have identified Anacardic acid (AA) as a potent inhibitor of gelatinases (MMP-2 and 9), which are over-expressed in a wide variety of cancers (Omanakuttan et al., 2012). Disruption of the finely tuned matrix metalloproteinase (MMP) activator/inhibitor balance plays a decisive role in determining the fate of the cell. The present study demonstrates for the first time, that in addition to regulating the expression as well as activity of gelatinases, AA also inhibits the expression of its endogenous activators like MMP-14 and Extracellular Matrix MetalloProteinase Inducer (EMMPRIN) and induces the expression of its endogenous inhibitor, REversion-inducing Cysteine-rich protein with Kazal motifs (RECK). In addition to modulating gelatinases, AA also inhibits the expression of various components of the Epidermal Growth Factor (EGF) pathway like EGF, Protein Kinase B (Akt) and Mitogen-activated protein kinases (MAPK). Furthermore, AA also activates the expression of Sprouty 2 (Spry2), a negative regulator of EGF pathway, and silencing Spry2 results in up-regulation of expression of gelatinases as well as MMP-14. The present study thus elucidates a novel mechanism of action of AA and provides a strong basis for utilizing this molecule as a template for cancer therapeutics.

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2016

Journal Article

Dr. Jyotsna Nambiar, Bose, C., Meera Venugopal, Dr. Asoke Banerji, Patel, T. B., Dr. Geetha Kumar, and Dr. Bipin G. Nair, “Anacardic acid inhibits gelatinases through the regulation of Spry2, MMP-14, EMMPRIN and RECK”, Experimental Cell Research, vol. 349, pp. 139-151, 2016.[Abstract]


Earlier studies from our laboratory have identified Anacardic acid (AA) as a potent inhibitor of gelatinases (MMP-2 and 9), which are over-expressed in a wide variety of cancers (Omanakuttan et al., 2012). Disruption of the finely tuned matrix metalloproteinase (MMP) activator/inhibitor balance plays a decisive role in determining the fate of the cell. The present study demonstrates for the first time, that in addition to regulating the expression as well as activity of gelatinases, AA also inhibits the expression of its endogenous activators like MMP-14 and Extracellular Matrix MetalloProteinase Inducer (EMMPRIN) and induces the expression of its endogenous inhibitor, REversion-inducing Cysteine-rich protein with Kazal motifs (RECK). In addition to modulating gelatinases, AA also inhibits the expression of various components of the Epidermal Growth Factor (EGF) pathway like EGF, Protein Kinase B (Akt) and Mitogen-activated protein kinases (MAPK). Furthermore, AA also activates the expression of Sprouty 2 (Spry2), a negative regulator of EGF pathway, and silencing Spry2 results in up-regulation of expression of gelatinases as well as MMP-14. The present study thus elucidates a novel mechanism of action of AA and provides a strong basis for utilizing this molecule as a template for cancer therapeutics.

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PDF iconanacardic-acid-inhibits-gelatinases-through-the-regulation-of-spry-2-mmp-14-emmprin-and-reck-11october2016.pdf

2015

Journal Article

Pandurangan Nanjan, Dr. Jyotsna Nambiar, Dr. Bipin G. Nair, and Dr. Asoke Banerji, “Synthesis and Discovery of (I-3,II-3)-Biacacetin as a Novel Non-zinc Binding Inhibitor of MMP-2 and MMP-9”, Bioorganic & Medicinal Chemistry, vol. 23, pp. 3781 - 3787, 2015.[Abstract]


Abstract Eleven biflavones (7a–b and 9a–i) were synthesised by a simple and efficient protocol and screened for MMP-2 and MMP-9 inhibitory activities. Amongst them, a natural product-like analog, (I-3,II-3)-biacacetin (9h) was found to be the most potent inhibitor. Molecular docking studies suggest that unlike most of the known inhibitors, 9h inhibits MMP-2 and MMP-9 through non-zinc binding interactions.

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PDF iconsynthesis-and-discovery-of-I-3-II-3-biacacetin-as-a-novel-non-zinc-binding-inhibitor-of-mmp-2-and-mmp-9-29march2015.pdf

2015

Journal Article

Dr. Jyotsna Nambiar, G., K., S.R., S., S.N., G., R.S., L., and Dr. Bipin G. Nair, “A Novel2-Alkoxy-3, 5-Dihydroxypyridine Mediated Regulation of Gelatinases”, International Journal of Pharma and Bio Sciences, vol. 6, pp. 779-788, 2015.

2012

Journal Article

A. Omanakuttan, Dr. Jyotsna Nambiar, Harris, R. M., Bose, C., Pandurangan Nanjan, Varghese, R. K., Kumar, G. B., Tainer, J. A., Dr. Asoke Banerji, J. Perry, J. P., and Dr. Bipin G. Nair, “Anacardic Acid Inhibits the Catalytic Activity of Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9”, 2012.[Abstract]


Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1′ pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC50 of 11.11 μM. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action.

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Publication Type: Conference Paper

Year of Publication Publication Type Title

2015

Conference Paper

Dr. Jyotsna Nambiar, Kumar, G. B., Pandurangan Nanjan, Dr. Asoke Banerji, and Dr. Bipin G. Nair, “Regulation of Gelatinases by (I-3,II-3)-Biacacetin, a Novel Non-zinc Binding Inhibitor of MMP-2 and MMP-9”, in The XXXIX All India Cell Biology Conference, 2015.[Abstract]


Gelatinases (MMP-2 and MMP-9) play a significant role in cancer progression by cleaving the major components of the extracellular matrix thereby promoting the migration of tumor cells. Majority of the MMP inhibitors reported are zinc chelating compounds which bind to the catalytic zinc via hydroxamate, carboxylate, thiol or phosphonic acid moieties. The extensive homology between catalytic domains of the MMPs makes these effective zinc binding inhibitors non-selective and toxic. To overcome such non selective toxicity, novel non-zinc binding MMP inhibitors have been developed.(I-3,II-3)-Biflavones form a small group of dimeric flavonoids which have not been extensively studied due to their limited occurrence. Among several differently substituted biflavones having hydroxy, methoxy, furano and cinnamyl moieties,(I-3,II-3)-biacacetin showed maximum inhibition of gelatinases without interfering with the zinc in the catalytic site.This novel non-zinc binding interaction of (I-3,II-3)-biacacetin was further confirmed by treating the cells with ZnCl2 along with(I-3,II-3)-biacacetin and showing that the inhibition remained unaffected even in the presence of ZnCl2.(I-3,II-3)-biacacetin showed significant reduction in migration of highly metastatic fibrosarcoma cell line, HT1080. The mechanism of (I-3,II-3)-biacacetinmediated modulation of cell migration through inhibition of gelatinases was further established by treating the cells with phorbol myristate acetate (PMA)along with (I-3,II-3)-biacacetinand using the same conditioned media for the migration assay. (I-3,II-3)-biacacetininhibitedPMA-stimulated gelatinase activity as well as migration of HT1080 cells in a concentration-dependent manner.These results suggests the use of (I-3,II-3)-biacacetin as a novel template for design and synthesis of analogswith improved potency and selectivity.

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2015

Conference Paper

D. G., Ashokan, L., Dr. Jyotsna Nambiar, Shaji, S. K., S, L., Kumar, G. B., and Dr. Bipin G. Nair, “In Vitro Culture of Primary Cells from Cancer Patients- Screening for Potent MMP-9 Inhibitors”, in The XXXIX All India Cell Biology Conference , 2015.[Abstract]


Breast cancer is the most prevalent form of cancer among women worldwide. Established cancer cell lines generated over years have been used for studying the biology of breast cancer. These cell lines which have been passaged innumerable times creates genetic drift which makes the observations biologically less relevant. In vitro culture of primary cells from fresh surgical specimens provides a more accurate means for understanding the behavior of cancer cells and the adjacent normal cells. We have developed a simple and rapid method for isolating primary cultures from breast tumor and normal cells. Two different methods were employed for isolating primary cultures- one involving enzymatic digestion and the other using explant culture which is independent of enzymatic treatment and feeder cells. The primary cells obtained were further characterized by immunocytochemistry staining for Vimentin and Cytokeratin 18. The cells stained positive for Vimentin and negative for Cytokeratin 18 which indicated that they are of mesenchymal origin. Since gelatinases play a prominent role in promoting breast cancer metastasis, the primary cells were assessed for gelatinase activity. Our observations clearly show that the cancer cells had up-regulated gelatinases activity compared to the adjacent normal cells. These cells when treated with several natural products showed a dose-dependent inhibition of gelatinase activity. The results obtained were consistent in all the primary cell lines generated from different patient samples. These studies with the primary cell lines will therefore help in obtaining biological responses that more accurately mimics the tumor/cancer micro environment.

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2013

Conference Paper

Dr. Jyotsna Nambiar, Kumar, G. B., and Nair, B. G., “Anacardic Acid regulates Gelatinases by modulation of MT1-MMP, TIMP-2 and EGF receptor signaling in Fibrosarcoma cells”, in Amrita Bioquest, 2013.

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