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Suparna Sengupta, PhD

Scientist E-II

+91-471-2529475

ssengupta@rgcb.res.in

suparna
suparna

Suparna Sengupta, PhD

Scientist E-II

+91-471-2529475

ssengupta@rgcb.res.in

  • Profile

    • Post-doctoral associate Biochemistry, University of Kansas, USA
    • Ph.D Biochemistry (Bose Institute, Calcutta)
    • M.Sc Chemistry (University of Calcutta)
    • B.Sc Chemistry (University of Calcutta)
    • 2012: Scientist EII, Rajiv Gandhi Centre for Biotechnology, Trivandrum
    • 2007: Visiting Scientist, Lehigh University, USA
    • 2005: Scientist EI, Rajiv Gandhi Centre for Biotechnology, Trivandrum
    • 2000: Scientist C, Rajiv Gandhi Centre for Biotechnology, Trivandrum
    • 1997: Pool-officer at National Institute of Immunology, New Delhi
    • Fellow, International Union Against Cancer
    • Fellow, Council of Scientific and Industrial Research through National Eligibility Test (NET)
    • 2007: International Union Against Cancer (UICC) International Study Grant to Lehigh University, Pennsylvania, USA
    • 2005: National Woman Bioscientist Award (Young Category), Department of Biotechnology (Government of India)
    • 2003: DR. V.B. Kamat Memorial Award from Indian Association of Cancer Research
    • Member, American Society for Cell Biology
    • Life Member, Indian Biophysical Society
    • Life Member, Society of Biotechnologists, India
    • Life Member, Kerala Science Academy
    • Ph.D Produced : 3
    • “A new solid phase method for the preparation of diaminoketothiazoles” Indian Patent 239492 (2004)
    • “DAT1, a synthetic diaminoketothiazole, its process of preparation and its use as a microtubule inhibitor, a probe for tubulin-microtubule system and a cytotoxic agent” PCT Application no. WO 2005/100332 A1
    • DAT1: SuparnaSengupta and K.N.Rajasekharan: US Patent US 8,158,806 B2
  • Research

    Study of Nucleation stage of microtubule assembly

    Shashikala S, Nisha Elizabeth Thomas, Rohit Kumar and Suparna Sengupta

    Microtubules are a major cytoskeletal component with many important functions. They are involved in cell division, maintenance of cell shape and polarity and transport of nutrients and organelles. Nucleation stage or the formation of oligomers is a crucial intermediate stage of microtubule assembly from its component proten tubulin. In a cell, improper nucleation may give rise to lack of polarity of interphase and mitotic cell, distorted shape and loss of directionality of microtubule mediated transport. Many proteins and antimitotic agents influence the nucleation stage of microtubule assembly.

    Gamma-tubulin associated proteins and their role in microtubule function

    Gamma tubulin is a major protein involved in the in vivo nucleation of microtubules. In the cells, gamma tubulin exists as a complex termed as the gamma tubulin ring complex in association with other proteins. It usually nucleates microtubules from the centrosomes. Gamma tubulin complex is also present in the cytoplasm, but seems to be transported to the centrosome before mitosis. The transport mechanism and the nucleation control mechanisms are unknown. We are trying to understand these complex mechanisms. The role of gamma tubulin complex proteins and its accessory proteins in modulating cellular functions are being studied in normal cells as well as in abnormal situations like cancer.

    Microtubule targeting compounds as potential anticancer agents

    Smreti Vasudevan, Reshma Thankachy, J.S. Sreeja and Suparna Sengupta

    Microtubules are one of the major cytoskeletal components which perform many functions. Due to their essential role in the spindle formation and chromosome separation, they are a popular target for anticancer drug development and some of them are widely used in the clinic. Microtubule binding compounds affect microtubule dynamics and the polymer stability, thereby giving rise to abnormal spindle leading the cells to a block in the G2/M phase, which normally get destined to apoptosis. Some of them affect the G2/M or spindle check point also thereby affecting their antimitotic property. Improper binding to tubulin and defective checkpoint control may give rise to resistance to anticancer drugs. By affecting microtubule dynamics, microtubule binding drugs may also act as antiangiogenic compounds as they alter the motility of endothelial cells and disrupt tumour vasculature. We are studying the mechanism of action of microtubule targeting novel cytotoxic compounds in cancer cells. The pathway leading to apoptosis after a mitotic block or aberrant mitotic exit is also being studied. Effort is on to develop a few promising compounds as anticancer drugs through cellular and animal models. The resistance mechanism of antimitotic compounds in cancer cells are also under study. We mostly use biochemical, biophysical and cell biology techniques for our study.

    Completed Research Projects as PI:

    Sl No. Title of Project Funding Agency Date of completion
    1 Structure-Function Studies of Diaminothiazoles, A New Class of Potential Anticancer Agent DST February 2012
    2 Interaction of a cytotoxic diaminothiazole with tubulin CSIR December 31, 2009
    3 Characterization of the Nucleation Stage of Microtubule Assembly by Some Assembly Inducers DST February 20, 2007
    4 Identification, Purification and Characterization of the ?-tubulin Complex from Indian Toad and its Involvement in Microtubule Nucleation Kerala State Council for Science, Technology & Environment August 13, 2006
  • Publications

    Publications 2012-2015

    1. Reshma Thamkachy, Rohith Kumar, K. N. Rajasekharan and Suparna Sengupta (2016) ERK mediated upregulation of death receptor 5 overcomes the lack of p53 functionality in the diaminothiazole DAT1 induced apoptosis in colon cancer models: efficiency of DAT1 in Ras-Raf mutated cells. Molecular Cancer 15:22 DOI 10.1186/s12943-016-0505-7 (Impact factor 4.2)
    2. Anasuya Ray, Smreti Vasudevan, Suparna Sengupta (2015) 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death. PLoS One. 10(9): e0137614. doi: 10.1371/journal.pone.0137614 (Impact factor 3.7)
    3. Smreti Vasudevan, Sannu Ann Thomas, Krishnankutty C. Sivakumar, Reena J. Komalam, Keerthi V. Sreerekha, Kallikat N. Rajasekharan and Suparna Sengupta (2015): Diaminothiazoles Evade Multidrug Resistance in Cancer Cells and Xenograft Tumour Models and Develop Transient Specific Resistance: Understanding the Basis of Broad-Spectrum vs Specific Resistance. Carcinogenesis Doi: 10.1093/ carcin/bgv072 (Impact factor: 5.266)
    4. Nisha E Thomas, Reshma Thamkachy, Krishnankutty C. Shivakumar, Sreedevi K.J., Xavier Lieben Louis,Sannu A. ThomasRohith Kumar, Kallikat N. Rajasekharan, Lynne Cassimeris & Suparna Sengupta* (2014): Reversible Action of Diaminothiazoles in Cancer Cells is Implicated by the Induction of a Fast Conformational Change of Tubulin and Suppression of Microtubule Dynamics. Molecular Cancer Therapeutics,  13, 179 – 189,DOI: 10.1158/1535-7163.MCT-13-0479 (Impact factor: 6.107)
    5. Mathan Sankaran,  Chokkalingam Uvarani, Kumarasamy Chandraprakash, Swathi U. Lekshmi, Sengupta Suparna,  James Platts, Palathurai Subramaniam Mohan (2014): A regioselective multicomponent protocol for the synthesis of novel bioactive 4-hydroxyquinolin-2(1H)-one grafted monospiropyrrolidine and thiapyrrolizidine hybrids. Molecular  Diversity DOI 10.1007/s11030-013-9498-y (Impact Factor 2.86)
    6. Sasidharan Shashikala, Rohith Kumar, Nisha E. Thomas, Dhanesh Sivadasan, Jackson James & Suparna Sengupta*  (2013): Fodrin in Centrosomes: Implication of a Role of Fodrin in the Transport of Gamma-Tubulin Complex in Brain. PLoS ONE 8(10): e76613. doi:10.1371/journal.pone.0076613 (Impact factor: 4.0)
    7. Sannu A. Thomas, Smreti Vasudevan, Reshma Thamkachy, Swathi U. Lekshmi, Thankayyan R. Santhoshkumar, Kallikat N. Rajasekharan & Suparna Sengupta* (2013): Upregulation of DR5 Receptor by the Diaminothiazole DAT1 [4-amino-5-benzoyl-2-(4-methoxy phenyl amino) thiazole] Triggers an Independent Extrinsic Pathway of Apoptosis in Colon Cancer Cells with Compromised Pro and Antiapoptotic Proteins: Apoptosis, 18, 713-726  (Impact factor: 4.8)
    8. S.Thalamuthu , B. Annaraj , Smerti Vasudevan , Suparna Sengupta & M.A. Neelakantan (2013): DNA binding, nuclease and colon cancer cell inhibitory activity of a Cu(II) complex of a thiazolidine-4-carboxylic acid derivative, Journal of Coordination Chemistry, DOI:10.1080/00958972.2013.791393 (Impact factor: 1.9)
    9. Sannu A. Thomas, Reshma Thamkachy, Bindu Ashokan,  Reena J. Komalam, Keerthi V. Sreerekha, Asha Bharathan, Thankayyan R. Santhoshkumar, Kallikat N. Rajasekharan and Suparna Sengupta* (2012): Diaminothiazoles Inhibit Angiogenesis Efficiently by Suppressing Akt Phosphorylation: Journal of Pharmacology and Experimental Therapeutics, 341, 718-724 (Impact factor: 4.1)

    Click here for more Publications

  • Team


    Anasuya Ray, DST Women Scientist

    Characterization of ginger extracted compound, 6-shogaol, as a potential anticancer agent against breast cancer

    Several studies have indicated the presence of cancer stem cells (CSC) in the proliferating cancer cell population. CSCs, although present as a minority of total cancer population, have immense self renewal capability and are thought to be the major source of tumor cell renewal. Presence of CSCs is a major obstacle for successful cancer chemotherapy because these cells regenerate new pool of rapidly proliferating cells. Besides, they often escape from the conventional chemotherapeutic agents. Thus targeting CSCs is thought to be a powerful strategy for complete eradication of cancer. While CSCs constitute a mere 1% of total tumor, methods have been developed to enrich them ex vivo in culture. I am investigating the role of ginger extracted compound, 6- shogaol in its ability to target cancer stem cells in breast cancer model and aim to determine the underlying mechanism in its anticancer activity

    anasuya
    anasuya

    Anasuya Ray, DST Women Scientist

    Characterization of ginger extracted compound, 6-shogaol, as a potential anticancer agent against breast cancer

    Several studies have indicated the presence of cancer stem cells (CSC) in the proliferating cancer cell population. CSCs, although present as a minority of total cancer population, have immense self renewal capability and are thought to be the major source of tumor cell renewal. Presence of CSCs is a major obstacle for successful cancer chemotherapy because these cells regenerate new pool of rapidly proliferating cells. Besides, they often escape from the conventional chemotherapeutic agents. Thus targeting CSCs is thought to be a powerful strategy for complete eradication of cancer. While CSCs constitute a mere 1% of total tumor, methods have been developed to enrich them ex vivo in culture. I am investigating the role of ginger extracted compound, 6- shogaol in its ability to target cancer stem cells in breast cancer model and aim to determine the underlying mechanism in its anticancer activity

    Smreti Vasudevan, PhD Student

    Mechanism of Resistance of Cancer Cells against Antimitotic Agents

    Antimitotic agents are widely used in cancer chemotherapy, especially for metastatic carcinomas. However after an apparently successful chemotherapy, acquired resistance to these agents is depressingly common. The resistance mechanisms evolved by cells against these agents is multifactorial and could involve enhanced efflux protein expression or target specific alterations at the level of tubulin isotypes, apoptotic proteins or spindle checkpoint anomalies. Their mechanistic complexity and intricacy makes antimitotic drug resistance still an incompletely understood arena. My work is focused on small tubulin binding agents which can be deployed in combating acquired resistance against clinically used drugs like taxol. Using drug resistant in vitro and xenograft tumour models we are trying to decipher the various drug resistance mechanisms evoked in cells by antimitotic agents which happen to be both drug and tissue specific. The potential of small molecules in evading drug resistance mechanisms is being explored.

    smreti
    smreti

    Smreti Vasudevan, PhD Student

    Mechanism of Resistance of Cancer Cells against Antimitotic Agents

    Antimitotic agents are widely used in cancer chemotherapy, especially for metastatic carcinomas. However after an apparently successful chemotherapy, acquired resistance to these agents is depressingly common. The resistance mechanisms evolved by cells against these agents is multifactorial and could involve enhanced efflux protein expression or target specific alterations at the level of tubulin isotypes, apoptotic proteins or spindle checkpoint anomalies. Their mechanistic complexity and intricacy makes antimitotic drug resistance still an incompletely understood arena. My work is focused on small tubulin binding agents which can be deployed in combating acquired resistance against clinically used drugs like taxol. Using drug resistant in vitro and xenograft tumour models we are trying to decipher the various drug resistance mechanisms evoked in cells by antimitotic agents which happen to be both drug and tissue specific. The potential of small molecules in evading drug resistance mechanisms is being explored.

    Reshma Thankachy, PhD Student

    Action of Diaminothaizoles in p53 Compromised Colon Cancer Models

    The p53 gene and its protein product have become the center of intensive study ever since it has been discovered that slightly more than 50% of human cancers contains mutation in this gene. p53 is a tumor suppressor gene and most of its tumor suppressor activity is due to its ability to function as a transcription factor. p53 can integrate various cellular stress signals from the cell and arrest the cell division or commit it to apoptosis. Since p53 gene is mutated in many cancers, any drug which is active in p53 mutated cancers will be of interest since it would be more tumor specific. Our earlier studies have established diaminothiazoles as efficient antimitotic, antiangiogenic and cytotoxic agents against different cancer cell lines. We have also shown that DAT1, a lead synthetic diaminothiazole, induces apoptosis in cancer cells and the apoptosis is mainly mediated by the death receptor DR5. My studies have revealed that DAT1 has a p53 independent mode of action. Studies in cell lines with compromised p53 and xenograft studies in Nod/Scid mice, are being done to know the mechanism of action of DAT1 in colon cancer model

    reshma1
    reshma1

    Reshma Thankachy, PhD Student

    Action of Diaminothaizoles in p53 Compromised Colon Cancer Models

    The p53 gene and its protein product have become the center of intensive study ever since it has been discovered that slightly more than 50% of human cancers contains mutation in this gene. p53 is a tumor suppressor gene and most of its tumor suppressor activity is due to its ability to function as a transcription factor. p53 can integrate various cellular stress signals from the cell and arrest the cell division or commit it to apoptosis. Since p53 gene is mutated in many cancers, any drug which is active in p53 mutated cancers will be of interest since it would be more tumor specific. Our earlier studies have established diaminothiazoles as efficient antimitotic, antiangiogenic and cytotoxic agents against different cancer cell lines. We have also shown that DAT1, a lead synthetic diaminothiazole, induces apoptosis in cancer cells and the apoptosis is mainly mediated by the death receptor DR5. My studies have revealed that DAT1 has a p53 independent mode of action. Studies in cell lines with compromised p53 and xenograft studies in Nod/Scid mice, are being done to know the mechanism of action of DAT1 in colon cancer model

    Rohit Kumar N, PhD Student

    Analysis of Fodrin Association with Gamma tubulin complex

    Gamma tubulin complex is known to be the nucleator of the microtubules in vivo in the form of gamma tubulin ring complex (g-TuRC). Brain g-TuRC have been shown to have an additional constituent, fodrin. Co-localization of fodrin with gamma tubulin in the centrosome has also been reported from our lab. Since fodrin localization is specifically confined to the brain cells, it is intriguing to look into the functional aspect of this association. I have identified the binding partner of fodrin within the complex and currently looking at the domain involved in this interaction. This might shed a light into the possible function of fodrin. I also intent to study the role of fodrin in the nucleation and organization of microtubules

    rohith photo
    rohith photo

    Rohit Kumar N, PhD Student

    Analysis of Fodrin Association with Gamma tubulin complex

    Gamma tubulin complex is known to be the nucleator of the microtubules in vivo in the form of gamma tubulin ring complex (g-TuRC). Brain g-TuRC have been shown to have an additional constituent, fodrin. Co-localization of fodrin with gamma tubulin in the centrosome has also been reported from our lab. Since fodrin localization is specifically confined to the brain cells, it is intriguing to look into the functional aspect of this association. I have identified the binding partner of fodrin within the complex and currently looking at the domain involved in this interaction. This might shed a light into the possible function of fodrin. I also intent to study the role of fodrin in the nucleation and organization of microtubules

    J S Sreeja, PhD Student

    Mapping the route from mitotic arrest to apoptosis

    Mitosis is a valued target of many anticancer drug therapies because the mitotic checkpoint is extremely stringent and acutely sensitive to irregularities. The foremost aim of my work would be to establish a possible link between the mitosis and apoptosis. Both these processes have a lot of morphological similarities in terms of chromatin compaction, destruction of the nuclear membrane and characteristic rounding up of the cells. But the molecular framework behind these processes is distinct. It therefore follows that there is definitive inter-regulatory connection between the two mechanisms. Noticeably, many apoptotic regulatory proteins are functionally modified in a cell cycle dependent manner. The upstream regulators of such modified proteins are probably the components of the mitotic checkpoint. The contribution of cell cycle kinases in the regulation of these proteins would be the major focus.

    sreeja
    sreeja

    J S Sreeja, PhD Student

    Mapping the route from mitotic arrest to apoptosis

    Mitosis is a valued target of many anticancer drug therapies because the mitotic checkpoint is extremely stringent and acutely sensitive to irregularities. The foremost aim of my work would be to establish a possible link between the mitosis and apoptosis. Both these processes have a lot of morphological similarities in terms of chromatin compaction, destruction of the nuclear membrane and characteristic rounding up of the cells. But the molecular framework behind these processes is distinct. It therefore follows that there is definitive inter-regulatory connection between the two mechanisms. Noticeably, many apoptotic regulatory proteins are functionally modified in a cell cycle dependent manner. The upstream regulators of such modified proteins are probably the components of the mitotic checkpoint. The contribution of cell cycle kinases in the regulation of these proteins would be the major focus.

  • Alumni