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T R Santhosh Kumar, PhD

Scientist E-II

+91-471-2781250

trsanthosh@rgcb.res.in

santhoshkumar
santhoshkumar

T R Santhosh Kumar, PhD

Scientist E-II

+91-471-2781250

trsanthosh@rgcb.res.in

  • Profile

    • Ph.D (Sree Chitra Thirunal Institute for Medical Sciences & Technology)
  • Research

    The thrust area of our research is to understand the molecular mechanisms of chemo resistance in cancer and develop interventional approaches for circumventing clinically relevant forms of drug resistance signaling encountered in solid tumours. Another important focus of the lab is to generate high through-put live cell based assays for identifying molecules that specifically attack key targets in cancer such as cell cycle, proteasome-Ubiquitin pathway, angiogenesis, HIF, tumour stem cells. The lab is involved in the Development of FRET based Optical imaging tools for non invasive preclinical drug screening employing near infrared and infrared fluorescent proteins as donors and acceptors.

  • Publications

    1. Mahendra Seervi, Praveen K. Sobhan, Jeena Joseph, Krupa Ann Mathew and T.R. Santhoshkumar, ERO1α-dependent endoplasmic reticulum-mitochondrial calcium flux contributes to ER stress and mitochondrial permeabilization by procaspase-activating compound-1 (PAC-1). Cell Death and Disease (2013) 4: e968; doi:10.1038/cddis.2013.502.
    2. Mahendra Seervi, Praveen K. Sobhan, Krupa Ann Mathew, Jeena Joseph, Prakash Rajappan Pillai, and T.R. Santhoshkumar, A high-throughput image based screen for the identification of bax/bak independent caspase activators against drug-resistant cancer cells. Apoptosis 2013 Nov 13: DOI 10.1007/s10495-013-0921-8.
    3. Vinitha Richard, Madhumathy G. Nair, T.R. Santhoshkumar and M. Radhakrishna Pillai, Side population cells as prototype of chemoresistant tumour-initiating cells. BioMed Res Inter 388 (2013) 300-316; http://dx.doi.org/10.1155/2013/517237.
    4. Vinitha Richard, Paul Sebastian, Madhumathy G. Nair, Sree Narayanan Nair, Tessy Thomas Malieckal, T.R. Santhoshkumar and M. Radhakrishna Pillai, Multiple drug resistant, tumorigenic stem-like cells in oral cancer. Cancer Letters 2013 http://dx.doi.org/10.1155/2013/517237.
    5. Praveen K. Sobhan, Mahendra Seervi, Lokesh Deb, Saneesh Varghese, Anjana Soman, Jeena Joseph, Krupa Ann Mathew, Godi Raghu, George Thomas, Sreekumar E., Manjula S. and T.R. Santhoshkumar, Caplain and reactive oxygen species targets Bax for mitochondrial permeabilisation and caspase activation in Zerumbone induced apoptosis. PLOS One 2013 8(4): e59350. doi:10.1371/journal.pone.0059350.
    6. Sannu A. Thomas, Smreti Vasudevan, Reshma Thamkachy, Swathi U. Lekshmi, Thankayyan R. Santhoshkumar, Kallikat N. Rajasekharan and Suparna Sengupta, 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 (2013), 18, 713-726.
    7. Mundackal Sivaraman Divya, Roshin Elizabeth George, Thulasi Sheela Divya, Vazhanthodi Abdul Rasheed, Retnabai Thankayyan Santhoshkumar, Kandathil Eapen Elizabeth, Jackson James and Radhakrishna M Pillai, Umbilical Cord blood derived mesenchymal stem cells consist of a unique population of progenitors co-expressing MSC and neuronal markers capable of instantaneous neuronal differentiation. Stem Cell Research & Therapy (2012) 3(6): 57; doi: 10.1186/scrt148.
    8. Sobhan PK, Seervi M, Joseph J, Varghese S, Pillai PR, Sivaraman DM, James J, George RE, Elizabeth KE, Santhoshkumar TR, Pillai MR. Immortalized functional endothelial progenitor cell lines from umbilical cord blood for vascular tissue engineering. Tissue Eng Part C Methods 18 (11): 890 – 902, 2012.
    9. Smitha Mohanlal, Sathish Kumar Maney, Thankayyan Retnabai Santhoshkumar, Ananthasankaran Jayalekshmy, Tricin 4′-O-(erythro-β-guaiacylglyceryl) ether and tricin 4′-O-(threo-β-guaiacylglyceryl) ether isolated from Njavara (Oryza sativa L. var. Njavara), induce apoptosis in multiple tumor cells by mitochondrial pathway. Journal of Natural Medicines , July 2013, 67(3), 528-533.
    10. Haneef J, Parvathy M, Thankayyan R SK, Sithul H, Sreeharshan S. Bax translocation mediated mitochondrial apoptosis and caspase dependent photosensitizing effect of Ficus religiosa on cancer cells. PLoS One 2012; 7(7): e40055. doi: 10.1371/journal.pone.0040055.
    11. Praveen KS, Seervi M, Joseph J, Bhavya BC, Varghese S, Santhoshkumar TR, Pillai MR. Identifcation of heat shock protein 90 inhibitors to sensitize drug resistant side population tumor cells using a cell based assay platform. Cancer Letters. 317:78–88, 2012.
    12. Sannu A. Thomas, Reshma Thamkachy, Bindu Ashokan, Reena J. Komalam, Keerthi V. Sreerekha, Asha Bharathan, Thankayyan R. Santhoshkumar, Kallikat N. Rajasekharan and Suparna Sengupta, Diaminothiazoles Inhibit Angiogenesis Efficiently by Suppressing Akt Phosphorylation, Journal of Pharmacology and Experimental Therapeutics (2012), 341, 718-724.
    13. B.C. Bhavya, Deepa Indira, Mahendra Seervi, Jeena Joseph, Praveen K. Sobhan, Krupa Ann Mathew, Saneesh Varghese and T.R. Santhoshkumar (2012). Endoplasmic reticulum-targeted Bcl-2 inhibitable mitochondrial fragmentation initiates ER stress-induced cell death. In: P.R. Sudhakaran and A. Surolia (eds.), Biochemical Roles of Eukaryotic Cell Surface Macromolecules, Advances in Experimental Medicine and Biology 749, Springer Science+Business Media, New York, chapter 7.
    14. Mohana Kumara P, Zuehlke S, Priti V, Ramesha BT, Shweta S, Ravikanth G, Vasudeva R, Santhoshkumar TR, Spiteller M, Uma Shaanker R. Fusarium proliferatum, an endophytic fungus from Dysoxylum binectariferum Hook.f, produces rohitukine, a chromane alkaloid possessing anti-cancer activity. Antonie Van Leeuwenhoek. 2011 Sep 4; DOI: 10.1007/s10482-011-9638-2.
    15. Mahendra Seervi, Jeena Joseph, Praveen K Sobhan, Bhavya BC, T R Santhosh Kumar, Essential Requirement of cytochrome c release for caspase activation by procaspase activating compound defined by cellular models. Cell Death Dis. 2011 Sep 8; 2:e207. doi: 10.1038/cddis.2011.90.
    16. Santhi Achuthan, T. R. Santhoshkumar, Jem Prabhakar, S. Asha Nair and M. Radhakrishna Pillai, Drug induced senescence generates chemoresistant stem like cells with low reactive oxygen species, Journal of Biological Chemistry. Published on August 30, 2011 as Manuscript M110.200675, http://www.jbc.org/cgi/doi/10.1074/jbc.M110.200675.
    17. S Sreeja, B S Lakshmi, T R Santhosh Kumar, S Sreeja. Pomegranate extract demonstrate a selective estrogen receptor modulator profile in human tumor cell lines and in vivo models of estrogen deprivation. Journal of Nutritional Biochemistry, DOI:10.1016/j.nutbio.2011.03.015.
    18. Sathish Kumar Maney, Ann Mary Johnson, A Sampath Kumar, Vineet Nair, T R Santhosh Kumar, C C Kartha; Effect of Apoptosis-Inducing Antitumor Agents on Endocardial Endothelial Cells. Cardiovasc Toxicol June 2011, DOI: 10.1007/s12012-011-9119-x.
    19. Jeena Joseph, Mahendra Seervi, Praveen K Sobhan, Santhoshkumar TR, High Throughput Ratio Imaging to Profile Caspase Activity: Potential Application in Multiparameter High Content Apoptosis Analysis and Drug Screening, PLoS ONE, 2011, 6(5): e20114 doi: 10.1371/journal.pone.0020114.
    20. Bhavya Balan Chandrikaa, Sathish Kumar Maney, Swathi U. Lekshmia and Santhoshkumar TR, Endoplasmic reticulum targeted Bcl2 confers long term cell survival through phosphorylation of heat shock protein 27. The International Journal of Biochemistry &Cell Biology Volume 42, Issue 12, December 2010, 1984-1992.
    21. NJ. Merlin, V. Parthasarathy and T R. Santhoshkumar, Induction of apoptosis in human breast cancer cell line MCF-7 by phytochemicals from Gmelina asiatica. Afr J Biotechnology Vol. 9 (28), pp. 4451-4456, 12 July, 2010.
    22. Bhavya Balan Chandrika, Sathish Kumar Maney, Swathi U. Lekshmi, Jeena Joseph,Mahendra Seervi, Praveen KS., Santhoshkumar T.R. Bax deficiency mediated drug resistance can be reversed by endoplasmic Reticulum stress induced death signaling , Biochemical Pharmacology 2010 Jun 1; 79(11):1589-99.
    23. Joy, Rajeev S, Emilia A, Mohan John, Praveen K.S., Mahendra Seervi, Santhoshkumar T.R., Lysosomal Destabilization and CathepsinB Contributes for Cytochrome C Release and Caspase activation in embelin induced apoptosis. Mol Carcinogenesis 2010 Apr; 49(4):324-36.
    24. Mohanakumar, P, Sreejayan N, Priti V, Ramesha BT, Ravikanth G, Ganeshaiah KN, Vasudeva R, Mohan J, Santhoshkumar TR, Mishra PD, Ram V, Shaanker RU., Dysoxylumbinectariferum Hook.f (Meliaceae), a rich source of rohitukine. Fitoterapia. 2010 Mar; 81(2):145-8.
    25. Kaur S, Kumar TR, Uruno A, Sugawara A, Jayakumar K, Kartha CC. Genetic engineering with endothelial nitric oxide synthase improves functional properties of endothelial progenitor cells from patients with coronary artery disease: an in vitro study. Basic Res Cardiol. 2009 Nov; 104(6):739-49.
    26. Raveendran R, Devi Suma Priya S, Mayadevi M, Steephan M, Santhoshkumar TR, Cheriyan J, Sanalkumar R, Pradeep KK, James J, Omkumar RV, Phosphorylation status of the NR2B subunit of NMDA receptor regulates its interaction with calcium/calmodulin-dependent protein kinase II. J Neurochem. 2009 Jul; 110(1):92-105.
    27. Paul BT, Babu MS, Santhoshkumar TR, Karunagaran D, Selvam GS, Brown K, Woo T, Sharma S, Naicker S, Murugesan R Biophysical evaluation of two red-shifted hypocrellin B derivatives as novel PDT agents. . J Photochem Photobiol B. 2009 Jan 9; 94(1):38-44.
    28. Kumar MA, Nair M, Hema PS, Mohan J, Santhoshkumar TR. Pinocembrin triggers Bax-dependent mitochondrial apoptosis in colon cancer cells. Mol Carcinog. 46(3):231-41 .2007.
    29. Kuruvilla L, Santhoshkumar T.R., Kartha CC. Immortalization and characterization of porcine ventricular endocardial endothelial cells. Endothelium. 14(1):35-43 .2007.
    30. Karunagaran D, Jeena Joseph, Kumar TR, Cell growth regulation, Adv Exp Med Biol, 2007, 595:245-68.
    31. John Mohan, Gandhi A, Bhavya BC, Rashmi, R, Karunagaran D, Indu R, Santhoshkumar T.R, caspase-2 triggers bax – bak dependent and independent cell death in colon cancer cells treated with resveratrol. J Biol Chem 281(26) 17599- 611 .2006.
    32. Sengupta, S., Smitha S.L, Thomas, N.E., Santhosh, T.R., Devi, C., Sreejalekshmi, K.G. and Rajasekharan, K.N. DAT1, A cytotoxic agent towards cancer cells and a probe for tubulin microtubule system. British J Pharmacology 145, 1076-1083 2005.
    33. Karunagaran, R. Rashmi and Santhosh Kumar T R. Induction of Apoptosis by Curcumin and Its Implications for Cancer Therapy. Current Cancer Drug Targets, 5, 117-129, 2005.
    34. Anshup J, Sai Venkataraman, Chandramouli Subramaniam, R. Rajeev Kumar, Suma Priya, T. R. Santhosh Kumar, R. V. Omkumar, Annie John, and T. Pradeep. Growth of Gold Nanoparticles in Human Cells. Langmuir 2005, 21, 11562-11567.
    35. Rashmi R, Santhosh Kumar T R, Karunagaran D.Human colon cancer cells lacking Bax resist curcumin-induced apoptosis and Bax requirement is dispensable with ectopic expression of Smac or downregulation of Bcl-xL. Carcinogenesis, 26, 4, 713-723, 2005.
    36. Rashmi R, Santhosh Kumar T R, Karunagaran D. Ectopic expression of Bcl-xL or Ku70 protects human colon cancer cells SW480 against curcumin induced apoptosis while their downregualtion potentiates it. Carcinogenesis vol.25 no.10 pp.1867–1877, 2004.
    37. Santhosh Kumar T R. Cytotoxicity and cell growth Assays. In: Selvin J, Ninave A.S (Eds.), Biotechnique, Biotech Consortia Tamil Nadu, India pp, 86-88.2003.
    38. Sengupta, S., Smitha S.L, Thomas, N.E., Santhosh Kumar T R, Devi, C. and Rajasekharan, K.N., DAT1, A Novel Synthetic Microtubule Inhibitor, Exerts Cytotoxicity and Shows Efficacy Towards Multidrug Resistant Cancer Cell. Mo. Biol Cell (Suppln) 14, 183a, 2003.
    39. Santhosh Kumar T R, Mary Vasantha Bai, Lissy K Krishnan. A freeze-dried fibrin disc as a biodegradable drug release matrix. Biologicals 32, 1, 49-55, 2004.
    40. Rashmi R, Santhosh Kumar T R, Karunagaran D. Ectopic expression of hsp 70 confersresistance and silencing its expression sensitizes Human colon cancer cells to curcumin-induced apoptosis. Carcinogenesis, 25(2), 179-187, 2004.
    41. Rashmi R, Santhosh Kumar T R, Karunagaran D.Human colon cancer cells differ in their sensitivity to curcumin induced apoptosis and heat shock protects them by inhibiting the release of apoptosis inducing factor. FEBS Letters, 13.538, 19-24, 2003.
    42. Santhosh Kumar T R and Lissy K. Krishnan. Fibrin mediated endothelial cell adhesion to vascular biomaterials to resist shear stress due to flow. Mater Science Materials in Medicine, 13, 1-5, 2002.
    43. Santhosh Kumar T R and Lissy K. Krishnan. A stable matrix for generation of tissue engineered non-thrombogenic vascular grafts. Tissue Engineering, 5, 763-70, 2002.
    44. Santhosh Kumar T R and Lissy K Krishnan. Endothelial cell growth factor enmeshed with polymerized fibrin to enhance proliferation of cell on polymeric materials. Biomaterials, 22, 2769-2776’ 2001.
    45. Umashankar PR, Santhosh Kumar TR, Arthur Vijayan Lal. Modified Xylazine-Ketamine injectable anaesthesia by atropine sulfate Diazepam premedication in Rabbits for bone implantation. Trends in Biomaterials and artificial Organs, 1, 27-36, 1996.
    46. Santhosh Kumar T R, Umashankar PR, Arthur Vijayan Lal. Effect of oxygen supplementation under xylazine – Ketamine anaesthesia in adult rats. Trends in Biomaterials and artificial Organs, 1, 44-48, 1996.
  • Team


    Abitha Murali, Post Doctoral Fellow (KSCSTE)

    NANOPARTICLE MEDIATED GENE SILENCING OF E6 GENES AND DOWNSTREAM SIGNALING IN HPV16 POSITIVE CERVICAL CARCINOMAS

    Cervical cancer remains the most common fatal cancer in Indian women. Although surgery and chemoradiotherapy can cure 80%–95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. Treatment strategies employing gene therapies are now being explored for treating cervical cancer. The therapeutic potential of siRNA-based therapeutics in cancer treatment has also been increasingly recognized, as numerous studies have shown the growth and proliferation of cancer cells can be greatly inhibited using this approach. Although small interfering RNAs (siRNAs) hold promise as nucleic acid-based therapeutics, effective and well-controlled in vivo delivery remains challenging as crossing biological barriers is difficult. Lipid nanoparticles have excellent biocompatibility, minimal toxicity, and are less costly comparing to polymeric carriers. In the present study, lipid nanoparticles harboring siRNA targeting HPV16 will be utilized to investigate downstream signaling and antitumor response both in in vitro and in vivo model.

    abitha_rgcb
    abitha_rgcb

    Abitha Murali, Post Doctoral Fellow (KSCSTE)

    NANOPARTICLE MEDIATED GENE SILENCING OF E6 GENES AND DOWNSTREAM SIGNALING IN HPV16 POSITIVE CERVICAL CARCINOMAS

    Cervical cancer remains the most common fatal cancer in Indian women. Although surgery and chemoradiotherapy can cure 80%–95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. Treatment strategies employing gene therapies are now being explored for treating cervical cancer. The therapeutic potential of siRNA-based therapeutics in cancer treatment has also been increasingly recognized, as numerous studies have shown the growth and proliferation of cancer cells can be greatly inhibited using this approach. Although small interfering RNAs (siRNAs) hold promise as nucleic acid-based therapeutics, effective and well-controlled in vivo delivery remains challenging as crossing biological barriers is difficult. Lipid nanoparticles have excellent biocompatibility, minimal toxicity, and are less costly comparing to polymeric carriers. In the present study, lipid nanoparticles harboring siRNA targeting HPV16 will be utilized to investigate downstream signaling and antitumor response both in in vitro and in vivo model.

    Deepa I, PhD student (CSIR-SRF)

    ROLE OF Bcl-2 FAMILY PROTEINS AND CASPASES IN ORGANELLE REMODELING DURING APOPTOSIS

    Apoptosis is accompanied by various morphological as well as biochemical changes of membrane bound structures such as mitochondria ,endoplasmic reticulum, golgi, lysosomes etc. Activation of caspases is the prime cause of these changes. Upstream caspases are activated through various internal and external stimuli leading to the activation of downstream caspases such as caspase 3 and caspase 7 which cleave many intracellular target proteins to induce apoptotic cell death. Most of the organellar changes are not well characterized and the order of these events is poorly understood. Studies shows that mitochondria, endoplasmic reticulum, golgi bodies are the sites of integration of cell death signals. However the significant role of most of the organelle remodeling in apoptotic cell death is not well appreciated. So it is hypothesized that there exists a correlation between various pro, anti -apoptotic proteins and enzymes in mediating the structural changes of these organelles. The aim of the present study is to expand our knowledge about the molecular events in the development of morphological alterations of organelles and to investigate these changes in the context of apoptotic cell death.

    deepa copy
    deepa copy

    Deepa I, PhD student (CSIR-SRF)

    ROLE OF Bcl-2 FAMILY PROTEINS AND CASPASES IN ORGANELLE REMODELING DURING APOPTOSIS

    Apoptosis is accompanied by various morphological as well as biochemical changes of membrane bound structures such as mitochondria ,endoplasmic reticulum, golgi, lysosomes etc. Activation of caspases is the prime cause of these changes. Upstream caspases are activated through various internal and external stimuli leading to the activation of downstream caspases such as caspase 3 and caspase 7 which cleave many intracellular target proteins to induce apoptotic cell death. Most of the organellar changes are not well characterized and the order of these events is poorly understood. Studies shows that mitochondria, endoplasmic reticulum, golgi bodies are the sites of integration of cell death signals. However the significant role of most of the organelle remodeling in apoptotic cell death is not well appreciated. So it is hypothesized that there exists a correlation between various pro, anti -apoptotic proteins and enzymes in mediating the structural changes of these organelles. The aim of the present study is to expand our knowledge about the molecular events in the development of morphological alterations of organelles and to investigate these changes in the context of apoptotic cell death.

    Krupa Ann Mathew, PhD Student (ICMR-SRF)

    HYPOXIA INDUCED SIGNALING IN CANCER STEM CELLS

    Human solid tumours often possess a hypoxic microenvironment. Hypoxic tumour cells are known to contribute to radio resistance, chemo resistance and increased metastasis. Many studies have shown cancer stem cells (CSC) or tumour-initiating cells (TIC) also to be therapy-resistant both in vitro and in vivo, resulting in tumour relapse and metastasis. Although much work has been done on tumour hypoxia and the expression of various hypoxia inducible genes via mediation of HIF-1, little information is known about the influence of hypoxia on tumour initiating cells. My study is aimed at identifying the molecular events operating in TICs as a result of hypoxia, culminating in therapy resistance. A major focus is to identify HIF alpha dependent and HIF alpha independent signaling cascades during hypoxic condition in tumor-initiating cells.

    krupa image
    krupa image

    Krupa Ann Mathew, PhD Student (ICMR-SRF)

    HYPOXIA INDUCED SIGNALING IN CANCER STEM CELLS

    Human solid tumours often possess a hypoxic microenvironment. Hypoxic tumour cells are known to contribute to radio resistance, chemo resistance and increased metastasis. Many studies have shown cancer stem cells (CSC) or tumour-initiating cells (TIC) also to be therapy-resistant both in vitro and in vivo, resulting in tumour relapse and metastasis. Although much work has been done on tumour hypoxia and the expression of various hypoxia inducible genes via mediation of HIF-1, little information is known about the influence of hypoxia on tumour initiating cells. My study is aimed at identifying the molecular events operating in TICs as a result of hypoxia, culminating in therapy resistance. A major focus is to identify HIF alpha dependent and HIF alpha independent signaling cascades during hypoxic condition in tumor-initiating cells.

    Asha Lekshmi, PhD student (ICMR-JRF)

    CELL CYCLE DEPENDENT CELL SIGNALING ANALYSIS

    Cell cycle involves an ordered series of macromolecular events that ends up in cell division and the production of two daughter cells. Regulation of the cell cycle is critical for the normal growth and development of multicellular organisms. This regulation is ensured by the combined action of multiple layers of signaling events within each cell. Loss of control over cell cycle ultimately leads to several diseases such as cancer. Although cancers are traditionally thought to be clonal, recent evidences point out intra-tumour heterogeneity in most cancers. Many studies have proved that both genetic and epigenetic alteration can bring heterogeneity in cell signaling responses. As cell cycle entry and progression involves oscillation of many signaling molecules, it is natural to think that cell cycle phases can influence heterogeneity in signaling. The major questions posed in my study are how are the different cell cycle phases influencing various signaling events? Development of appropriate tools for analysing the heterogeneity in different signaling responses such as calcium signaling, pH signaling, Reactive Oxygen Species (ROS) signaling, cell death and survival signaling etc. in a cell cycle dependent manner using multidimensional time-lapse imaging approach? What are the key regulators that drive cell cycle dependent signaling diversity in cells?

    Asha
    Asha

    Asha Lekshmi, PhD student (ICMR-JRF)

    CELL CYCLE DEPENDENT CELL SIGNALING ANALYSIS

    Cell cycle involves an ordered series of macromolecular events that ends up in cell division and the production of two daughter cells. Regulation of the cell cycle is critical for the normal growth and development of multicellular organisms. This regulation is ensured by the combined action of multiple layers of signaling events within each cell. Loss of control over cell cycle ultimately leads to several diseases such as cancer. Although cancers are traditionally thought to be clonal, recent evidences point out intra-tumour heterogeneity in most cancers. Many studies have proved that both genetic and epigenetic alteration can bring heterogeneity in cell signaling responses. As cell cycle entry and progression involves oscillation of many signaling molecules, it is natural to think that cell cycle phases can influence heterogeneity in signaling. The major questions posed in my study are how are the different cell cycle phases influencing various signaling events? Development of appropriate tools for analysing the heterogeneity in different signaling responses such as calcium signaling, pH signaling, Reactive Oxygen Species (ROS) signaling, cell death and survival signaling etc. in a cell cycle dependent manner using multidimensional time-lapse imaging approach? What are the key regulators that drive cell cycle dependent signaling diversity in cells?

    Shankara Narayanan V, PhD Student (UGC-JRF)

    CELL CYCLE AND CELL DEATH REGULATION IN TUMOR STEM CELLS

    Cancer is one of the most dreaded and ever growing diseases of mankind. The existing therapies of cancer generally target the bulk of the tumor. However, it has been noted that the small surviving fractions of the tumor play a major role in tumor recurrence. This may be attributed to the tumor stem cells. Tumor stem cells are characterized by the presence of several surface markers and functional traits. A unique functional property of tumor stem cells is quiescence or low cycling. However cancer in general is characterized by aggressive proliferation of cells. Hence the tumor cells with stem cell properties are hypothesized to have differential regulation of cell cycle than bulk tumor cells. The core concept of the proposal is to identify the regulatory mechanisms of cell cycle and cell death/survival signaling in tumor stem cells.

    Shankar
    Shankar

    Shankara Narayanan V, PhD Student (UGC-JRF)

    CELL CYCLE AND CELL DEATH REGULATION IN TUMOR STEM CELLS

    Cancer is one of the most dreaded and ever growing diseases of mankind. The existing therapies of cancer generally target the bulk of the tumor. However, it has been noted that the small surviving fractions of the tumor play a major role in tumor recurrence. This may be attributed to the tumor stem cells. Tumor stem cells are characterized by the presence of several surface markers and functional traits. A unique functional property of tumor stem cells is quiescence or low cycling. However cancer in general is characterized by aggressive proliferation of cells. Hence the tumor cells with stem cell properties are hypothesized to have differential regulation of cell cycle than bulk tumor cells. The core concept of the proposal is to identify the regulatory mechanisms of cell cycle and cell death/survival signaling in tumor stem cells.

    Santhik SL, PhD student (CSIR-JRF)

    SEARCH FOR SIGNALING EVENTS THAT CONTRIBUTE TO DRUG ESCAPE DURING CHEMOTHERAPY

    Recurrence of tumour after chemotherapy or radiotherapy impedes successful cancer treatment. Our initial studies suggest that molecular events related to emergence of drug resistant cells after chemotherapy is associated with reactivation of antioxidant defense signaling which help in the transition of these cells from high ROS to low ROS state. But the key molecular events that contribute to the immediate cell survival after a lethal dose of drug is poorly understood. So the current study focuses on the key signaling pathway and the molecules associated with the immediate survival of cancer cells during chemotherapy. Cancer cell lines of different origin were stably expressed with fluorescent sensors of apoptosis, autophagy and mitophagy will be analysed to understand key pathway that drive the cells to escape from extreme stress condition.

    Santhik
    Santhik

    Santhik SL, PhD student (CSIR-JRF)

    SEARCH FOR SIGNALING EVENTS THAT CONTRIBUTE TO DRUG ESCAPE DURING CHEMOTHERAPY

    Recurrence of tumour after chemotherapy or radiotherapy impedes successful cancer treatment. Our initial studies suggest that molecular events related to emergence of drug resistant cells after chemotherapy is associated with reactivation of antioxidant defense signaling which help in the transition of these cells from high ROS to low ROS state. But the key molecular events that contribute to the immediate cell survival after a lethal dose of drug is poorly understood. So the current study focuses on the key signaling pathway and the molecules associated with the immediate survival of cancer cells during chemotherapy. Cancer cell lines of different origin were stably expressed with fluorescent sensors of apoptosis, autophagy and mitophagy will be analysed to understand key pathway that drive the cells to escape from extreme stress condition.

    Gin Alexander, Junior Research Fellow

    Design and development of new generation caspase sensor FRET probe expressing stable cancer cells for anticancer drug screening : From in-vitro HTS screen to whole animal imaging

    Developing better therapies against cancer requires highly sensitive and better screening approaches to test the property of a drug from preliminary screening to the preclinical efficacy evaluation. The agents inducing apoptosis are generally accepted to perform better against cancer cells. So, accurate and sensitive detection of apoptosis has become crucial for evaluating these agents. As activation of caspases is key feature in apoptosis, so, monitoring the caspase activation in live cell using FRET probes of donor and acceptor fluorophores linked with activated caspase specific sequence in between is employed in recent years. Generally, most of the donors and acceptors presently used like ECFP/EYFP or EGFP are sensitive for in-vitro assay but not amenable for whole animal in-vivo optical imaging due to poor penetration, interference, scatterings etc. So we propose to employ new generation red shifted fluorescent proteins as donors and far red shifted fluorescent protein as acceptors for the development of optical imaging probe for caspase activation in cancer cell lines. The stable cells expressing such new generation probes will be evaluated for in-vitro caspase screening and preclinical drug testing in whole animal using optical imaging approaches.

    Gin photo
    Gin photo

    Gin Alexander, Junior Research Fellow

    Design and development of new generation caspase sensor FRET probe expressing stable cancer cells for anticancer drug screening : From in-vitro HTS screen to whole animal imaging

    Developing better therapies against cancer requires highly sensitive and better screening approaches to test the property of a drug from preliminary screening to the preclinical efficacy evaluation. The agents inducing apoptosis are generally accepted to perform better against cancer cells. So, accurate and sensitive detection of apoptosis has become crucial for evaluating these agents. As activation of caspases is key feature in apoptosis, so, monitoring the caspase activation in live cell using FRET probes of donor and acceptor fluorophores linked with activated caspase specific sequence in between is employed in recent years. Generally, most of the donors and acceptors presently used like ECFP/EYFP or EGFP are sensitive for in-vitro assay but not amenable for whole animal in-vivo optical imaging due to poor penetration, interference, scatterings etc. So we propose to employ new generation red shifted fluorescent proteins as donors and far red shifted fluorescent protein as acceptors for the development of optical imaging probe for caspase activation in cancer cell lines. The stable cells expressing such new generation probes will be evaluated for in-vitro caspase screening and preclinical drug testing in whole animal using optical imaging approaches.

    Prakash R, Technical Assistant

    The current job includes maintenance of the central cell line facility and the research project involving development of stable cells to be used for cell based assays. Routine work involves large scale expansion, freezing, long term maintenance of the cells and quality check. Additionally, operation and maintenance of the equipments such as automated microscopy, live cell imaging units, spinning disc Confocal imager, high throughput live cell imaging are part of the assigned job.

    Prakash
    Prakash

    Prakash R, Technical Assistant

    The current job includes maintenance of the central cell line facility and the research project involving development of stable cells to be used for cell based assays. Routine work involves large scale expansion, freezing, long term maintenance of the cells and quality check. Additionally, operation and maintenance of the equipments such as automated microscopy, live cell imaging units, spinning disc Confocal imager, high throughput live cell imaging are part of the assigned job.

    Vijith V, Project Trainee

    The current job profile includes development and maintenance of cell lines at the central cell line facility RGCB. The job also includes the operation of various microscopes and other instruments for cell imaging and various other works. Current work also includes high throughput screening of compound libraries using cell based tools for diverse targets in cancer cells such as HIF, NRF2, Cell cycle and apoptosis.

    vijith
    vijith

    Vijith V, Project Trainee

    The current job profile includes development and maintenance of cell lines at the central cell line facility RGCB. The job also includes the operation of various microscopes and other instruments for cell imaging and various other works. Current work also includes high throughput screening of compound libraries using cell based tools for diverse targets in cancer cells such as HIF, NRF2, Cell cycle and apoptosis.

  • Alumni