Profile

Research

Publications

Team

Alumni

S Asha Nair, PhD

Scientist E-II

+91-471-2529501

sasha@rgcb.res.in

asha
asha

S Asha Nair, PhD

Scientist E-II

+91-471-2529501

sasha@rgcb.res.in

  • Profile

    • Ph.D Tumor Biology, Regional Cancer Centre, University of Kerala (1993-1997)
    • M.Sc Zoology, College for Women, Thiruvananthapuram, University of Kerala (1990-1992)
    • B.Sc Zoology, St Joseph’s College, Vishakapatnam, Andhra University (1987-1990)
    • 2011 January 5th – till date, Scientist EII, Cancer Research Program, RGCB
    • 2006 January 5th – 2010, Scientist EI, Cancer Research Program, RGCB
    • 2005 – Clayton Foundation Post-Doctoral fellowship in the Dept of Experimental Therapeutics, MD Anderson Cancer Centre, Houston, Texas, USA
    • 2004 – Research Fellowship in the Dept of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, USA
    • 2002 : SERC Fast Track Proposals for Young Scientist 2001-2002 Scheme from DST, Govt. of India as Principal Investigator of the study
    • 1999 : Research Associateship / Post Doctral Fellowship from CSIR in Rajiv Gandhi Centre for Biotechnology (RGCB)
    • 1995-1997 : Senior Research Fellowship from CSIR
    • 1993-1995 : Junior Research Fellowship from Council of Scientific and Industrial Research (CSIR), India
    • 1993 : Third Rank for MSc Zoology from Kerala University
    • Member, Society of Biological Chemists
    • Life Member, Indian Association for Cancer Research (IACR)
    • Life Member, Society for Biotechnologists – India
    • Life Member, American Association for Cancer Research (AACR)
    • Patent titled “Novel porphyritic derivatives for photo dynamic therapy (PDT): A process for the preparation and thereof and their use as PDT agents and fluorescence probes for biological applications”, D. Ramaiah, S. C. Karunakaran, V. S. Jisha, T. K. Chandrashekar, A. Sreenivasan, M. R. Pillai, S. A. Nair, S. B. P. Saras, C. M. Rao, K. S. Rao., Dated 14-Sep-2009 (Ref. No. 0147NF2009)
  • Research

    MAJOR AREAS OF RESEARCH

    MOLECULAR CANCER RESEARCH
    1. E3 Ubiquitin ligase
    2. PAK-1 in pancreatic cancer-Collaboration: IIT, Chennai
    3. Role of PPAR g in cancer progression
    CANCER STEM CELL IN SOLID TUMORS
    1. Cancer stem like cells in colorectal cancer drug resistance (EMR grant-DBT)
      Collaboration: RCC, Tvpm
    2. MTA-1 in Endometrial cancer stem like cells and Invasion Collaboration: RCC, Tvpm
    TRANSLATIONAL – THERAPEUTICS
    1. PDT in cancer (EMR grant-DST) Collaboration: NIIST, Tvpm
    2. Nanoparticle mediated drug delivery (EMR grant-DBT) Collaboration-Chemical Biology RGCB
    3. Indirubins inhibiting E3 Ligases in CML

    COLLABORATORS NATIONAL & INTERNATIONAL

    1. Dr. Suresh Rayala, Associate Professor, Dept. Of Biotechnology, IIT Chennai
    2. Dr.D. Ramaiah, Scientist EII – NIIST Tvpm.
    3. Dr. Srinivas NIISER Bhuvaneswar, Orrisa
    4. Dr. Vinod Kumar .G. Scientist, Chemical Biology, RGCB
    5. Dr. Ajaikumar Kunnumakkara, Associate Professor, IIT Guwahati
    6. Dr. Chandramohan.K, Associate Professor, Surgical Oncology, Regional Cancer Centre, Tvpm
    7. Dr. Jem Prabhakar , Associate Professor, Surgical Oncology, Regional Cancer Centre, Tvpm
    8. Dr. Kalesh, MCH, Surgeon, Medical College, Tvpm
    9. Dr Alan Prem Kumar, Research Assistant Professsor, Dept of Pharmacology, NUS, SINGAPORE
    10. Dr. Vinay Tergoankar, Senior Principal Investigator, Institute of Molecular and Cell Biology, SINGAPORE
  • Publications

    Publications 2011 onwards

    1. Diana David, Lakshmy M R, Balachandran K, Jissa V T, Nair AS*, Pillai M R (2011) Prognostic significance of STAT3 and phosphorylated STAT3 in human soft tissue tumors – a clinicopathological analysis. Journal of Experimental & Clinical Cancer Research, 30:56
    2. Nair L.K, Jagadeeshan S, Asha Nair S, Kumar G.S.V (2011). Biological evaluation of 5-Fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA. International Journal of Nanomedicine, 6: 1685–1697
    3. Achuthan. S, Santhoshkumar T.R, Prabhakar J, Nair SA, Pillai M. R (2011). Drug induced senescence generates chemoresistant stem like cells with low reactive oxygen species. Journal of Biological Chemistry 43: 37813-37829.
    4. Nair L.K, Jagadeeshan S, Asha Nair S, Kumar G.S.V (2011). Evaluation of triblock copolymeric micelles of δ- Valerolactone and poly (ethylene glycol) as a competent vector for doxorubicin delivery against cancer. Journal of Nanobiotechnology 9: 42
    5. Babykutty S, Suboj P, Srinivas P, Nair AS, Srinivas G. (2012) Insidious role of nitric oxide in migration/invasion of colon cancer cells by upregulating MMP-2/9 via activation of cGMP-PKGERK signaling pathways. Clin Exp Metastasis. 5 :471-92
    6. Simon A M, Jagadeeshan S, Abraham E, Ashalatha. A,. Pillai, J,. Kumar N A, Nair. A S, Kumar G.S.V (2012) Poly (D,L-lactic-co-glycolide) nanoparticles for the improved therapeutic efficacy of all-trans-retinoic acid: A study of acute myeloid leukemia (AML) cell differentiation in vitro. Medicinal Chemistry 8,805-810
    7. Thomas AP, Saneesh Babu PS, Asha Nair S, Ramakrishnan S, Ramaiah D, Chandrashekar TK, Srinivasan A, Radhakrishna Pillai M (2012) meso-Tetrakis(p-sulfonatophenyl)N-Confused Porphyrin Tetrasodium Salt: A Potential Sensitizer for Photodynamic Therapy. J Med Chem. 55(11):5110-20.
    8. Anand Krishnan, Johnson A, Gopinath VR, Nair AS*, Pillai MR (2013) Cell cycle analysis and MN induction frequency reveals G0/G1 blockers to be weak MN inducers Drug and Chemical Toxicology 36(2):249-54
    9. Ashwani N, Kumar N A, Nair. A S, Kumar G.S.V. Pillai M.R (2012) Methacrylic based nanogel for the pH sensitive delivery of 5-Flourouracil. International Journal of Nannomedicine 7, 5769-5779
    10. Suneesh C. Karunakaran, P. S. Saneesh Babu, Bollapalli Madhuri, Betsy Marydasan, Albish K. Paul, S. Asha Nair, K. Sridhar Rao, A. Srinivasan, Tavarekere K. Chandrashekar, Ch. Mohan Rao,* M. Radhakrishan Pillai,* and Danaboyina Ramaiah (2013). In Vitro Demonstration of Apoptosis Mediated Photodynamic Activity and NIR Nucleus Imaging through a Novel Porphyrin ACS Chemical Biology ;8(1):127-32
    11. Diana David, Asha .S. Nair*, Pillai MR (2013). Smurf E3 Ubiquitin Ligases at the Cross Roads of Oncogenesis and Tumor Suppression. BBA Reviews On Cancer 1835(1):119-28
    12. Krishnan, Anand, Vivek R. Gopinath, Ajit Johnson, S. Asha Nair, and M. Radhakrishna Pillai. “Cell-cycle analysis and micronuclei frequency reveals G0/G1 blockers as weak micronuclei inducers.” Drug Chem Toxicol. 2013 Apr;36(2):249-54
    13. Jagadeeshan S, Krishnamoorthy YR, Singhal M, Subramanian A, Mavuluri J, Lakshmi A, Roshini A, Baskar G, Ravi M, Joseph LD, Sadasivan K,Krishnan A, Nair AS, Venkatraman G, Rayala SK (2014) Transcriptional regulation of fibronectin by p21-activated kinase-1 modulates pancreatic tumorigenesis Oncogene. Feb 24. doi: 10.1038/onc.2013.576. [Epub ahead of print]
    14. Ashwanikumar, N, Nisha Asok Kumar, Asha Nair S and GS Vinod Kumar Phenylalanine containing self-assembling peptide nanofibrous hydrogel for the controlled release of 5-fluorouracil and Leucovorin RSC Adv., 2014, Accepted Manuscript 10 Jun 2014 DOI: 10.1039/C4RA04393F
  • Team


    Diana David, PhD Student

    The highly conserved eukaryotic ubiquitin-proteasome system plays a pivotal role in protein homeostasis and is critical in regulating normal and cancer related cellular processes. The specificity and selectivity of target proteins for degradation are defined by particular E3 ubiquitin ligases. Several oncogenic E3 ubiquitin ligases have been identified as diagnostic markers or potential drug targets in human breast cancer. Smad ubiquitin regulatory factors (Smurfs) belong to the HECT- family of E3 ubiquitin ligases and comprise mainly of two members, Smurf1 and Smurf2. Initially, Smurfs have been implicated in determining the competence of cells to respond to TGF-β/BMP signalling pathway. Notably, aberrant expression of SMURF2 occurs in several types of cancers, including breast, esophageal, pancreatic and renal cell carcinomas. Nevertheless, the intrinsic catalytic activity has extended the repertoire of Smurf substrates beyond the TGF-β/BMP super family expanding its realm further to epigenetic modifications of histones governing the chromatin landscape. The present study was done to analyse the specific role of Smurf2 in regulating breast cancer cell proliferation and to identify the potential molecular targets implicated in these functions along with SMURF2.
    In our study we identified a possible interaction between SMURF2 and CNKSR2 (connector enhancer of kinase suppressor of Ras 2), a scaffold protein involved in Ras signalling pathway. CNKSR2 and its homolog CNKSR1 was found to play an important role in regulating cell proliferation via the MAPK, PI3K-AKT and NF-κB pathway. Hence, studying the potential interaction between SMURF2 and CNKSR2 might pave the way to understand the role of SMURF2 in maintaining cellular homeostasis.

    diana
    diana

    Diana David, PhD Student

    The highly conserved eukaryotic ubiquitin-proteasome system plays a pivotal role in protein homeostasis and is critical in regulating normal and cancer related cellular processes. The specificity and selectivity of target proteins for degradation are defined by particular E3 ubiquitin ligases. Several oncogenic E3 ubiquitin ligases have been identified as diagnostic markers or potential drug targets in human breast cancer. Smad ubiquitin regulatory factors (Smurfs) belong to the HECT- family of E3 ubiquitin ligases and comprise mainly of two members, Smurf1 and Smurf2. Initially, Smurfs have been implicated in determining the competence of cells to respond to TGF-β/BMP signalling pathway. Notably, aberrant expression of SMURF2 occurs in several types of cancers, including breast, esophageal, pancreatic and renal cell carcinomas. Nevertheless, the intrinsic catalytic activity has extended the repertoire of Smurf substrates beyond the TGF-β/BMP super family expanding its realm further to epigenetic modifications of histones governing the chromatin landscape. The present study was done to analyse the specific role of Smurf2 in regulating breast cancer cell proliferation and to identify the potential molecular targets implicated in these functions along with SMURF2.
    In our study we identified a possible interaction between SMURF2 and CNKSR2 (connector enhancer of kinase suppressor of Ras 2), a scaffold protein involved in Ras signalling pathway. CNKSR2 and its homolog CNKSR1 was found to play an important role in regulating cell proliferation via the MAPK, PI3K-AKT and NF-κB pathway. Hence, studying the potential interaction between SMURF2 and CNKSR2 might pave the way to understand the role of SMURF2 in maintaining cellular homeostasis.

    Saneesh Babu P S, PhD Student

    Photodynamic therapy (PDT) is a promising cancer treatment modality. It involves targeted tumour destruction by the combined action of light and drugs called photosensitizers and this process is called photodynamic therapy. It can be used for drug-resistant tumors and in patients with conditions forbidding surgery. However, there is a critical need for better exogenous PDT sensitizers. We set our preliminary objectives to develop efficient photosensitizers that become activated in the NIR region based on squaraine, croconaine and expanded porphyrins and their metal complexes. These compounds were synthesized by our chemist colleagues at National Institute for Interdisciplinary Science and Technology led by Dr.D.Ramaiah. We initially studied in vitro photodynamic efficacy on sixteen compounds and found four of them to be potential photosensitizers in NIR region. Further validation by in vivo photodynamic experiments is being completed for taking these compounds to pre-clinical trials.
    Photodynamic therapy primarily results in a sequence of photochemical events that generate reactive oxygen species (ROS), which induce oxidative damage ultimately causing the killing of cancerous cells or other targets of therapeutic interest .Because of limited light penetration through tissues (resulting from its absorption, scattering and reflection), the antitumor effects of PDT are limited to just a few centimetres. Deeper layers of the tumor receive light doses that are ineffective to fully excite the photosensitizers. Sublethal damage to tumor cells and the vasculature is therefore readily managed by constitutive or induced protective mechanisms. The surviving cells might be the cause of relapse rendering the treatment less effective. Therefore, elucidation of these protective mechanisms, molecular changes in the treated cells as well as identification of drugs that might interfere with rescue responses becomes an important area of our investigation.

    s1
    s1

    Saneesh Babu P S, PhD Student

    Photodynamic therapy (PDT) is a promising cancer treatment modality. It involves targeted tumour destruction by the combined action of light and drugs called photosensitizers and this process is called photodynamic therapy. It can be used for drug-resistant tumors and in patients with conditions forbidding surgery. However, there is a critical need for better exogenous PDT sensitizers. We set our preliminary objectives to develop efficient photosensitizers that become activated in the NIR region based on squaraine, croconaine and expanded porphyrins and their metal complexes. These compounds were synthesized by our chemist colleagues at National Institute for Interdisciplinary Science and Technology led by Dr.D.Ramaiah. We initially studied in vitro photodynamic efficacy on sixteen compounds and found four of them to be potential photosensitizers in NIR region. Further validation by in vivo photodynamic experiments is being completed for taking these compounds to pre-clinical trials.
    Photodynamic therapy primarily results in a sequence of photochemical events that generate reactive oxygen species (ROS), which induce oxidative damage ultimately causing the killing of cancerous cells or other targets of therapeutic interest .Because of limited light penetration through tissues (resulting from its absorption, scattering and reflection), the antitumor effects of PDT are limited to just a few centimetres. Deeper layers of the tumor receive light doses that are ineffective to fully excite the photosensitizers. Sublethal damage to tumor cells and the vasculature is therefore readily managed by constitutive or induced protective mechanisms. The surviving cells might be the cause of relapse rendering the treatment less effective. Therefore, elucidation of these protective mechanisms, molecular changes in the treated cells as well as identification of drugs that might interfere with rescue responses becomes an important area of our investigation.

    Chithra J S, PhD Student

    Endometriosis and endometrial cancer are pathologic conditions of human endometrium. Endometriosis is a common gynecological disorder that is characterized by the growth of hormone responsive endometrial tissue outside the uterine cavity. It is associated with local inflammation and the distressing symptoms of chronic pelvic pain as well as infertility. An increased risk of gynecological cancer is found in endometriotic patients. Many theories have been proposed to explain the etiology of endometriosis but it still remains enigmatic.The currently favoured theory is the retrograde menstruation theory which suggests that viable endometrial cells, shed from the endometrium into the pelvic cavity by retrograde menstruation, reattach and invade other tissues causing endometriosis. Retrograde menstruation occurs in most menstruating women however only 6-10% of women develop endometriosis. This might be because of the difference in the invasive property of the viable endometrial cells. In endometrial carcinoma the glandular epithelium undergoes uncontrolled proliferation and invades the surrounding connective tissue. Deep myometrial infiltration is a factor associated with poor prognosis in endometrial cancer patients. Several studies show that the cells undergoing invasion in cancer and endometriosis possess stem cell characteristics which have the ability to differentiate in to the tissue of origin. However the mechanism of invasion by stem cells is not explored in detail till now. We believe that deregulation of the key signalling pathways associated with endometrial stem cells might be involved in endometriosis and its transition to aggressive malignancies. We intend to study these alterations in stem cells of primary endometrial samples collected from endometriotic and endometrial cancer patients.

    chitra
    chitra

    Chithra J S, PhD Student

    Endometriosis and endometrial cancer are pathologic conditions of human endometrium. Endometriosis is a common gynecological disorder that is characterized by the growth of hormone responsive endometrial tissue outside the uterine cavity. It is associated with local inflammation and the distressing symptoms of chronic pelvic pain as well as infertility. An increased risk of gynecological cancer is found in endometriotic patients. Many theories have been proposed to explain the etiology of endometriosis but it still remains enigmatic.The currently favoured theory is the retrograde menstruation theory which suggests that viable endometrial cells, shed from the endometrium into the pelvic cavity by retrograde menstruation, reattach and invade other tissues causing endometriosis. Retrograde menstruation occurs in most menstruating women however only 6-10% of women develop endometriosis. This might be because of the difference in the invasive property of the viable endometrial cells. In endometrial carcinoma the glandular epithelium undergoes uncontrolled proliferation and invades the surrounding connective tissue. Deep myometrial infiltration is a factor associated with poor prognosis in endometrial cancer patients. Several studies show that the cells undergoing invasion in cancer and endometriosis possess stem cell characteristics which have the ability to differentiate in to the tissue of origin. However the mechanism of invasion by stem cells is not explored in detail till now. We believe that deregulation of the key signalling pathways associated with endometrial stem cells might be involved in endometriosis and its transition to aggressive malignancies. We intend to study these alterations in stem cells of primary endometrial samples collected from endometriotic and endometrial cancer patients.

    Dhanya K, PhD Student

    Forkhead box (Fox) proteins are family of evolutionarily conserved transcriptional regulators, which control a wide spectrum of biological processes. A loss or gain of Forkhead proteins function can alter cell fate and promote tumorigenesis as well as cancer progression. Foxm1 is known to regulate the genes important for G1/S-transition, S-phase progression, G2/M transition and progression through M-phase. Abnormal up regulation of FoxM1 has been reported in majority of solid human cancers including liver, breast, lung, prostate, cervix, colon, pancreas and brain.
    Previous studies from our lab reported that, increased expression of CDK1 occurred when SKP2, an E3 ubiquitin ligase was over expressed. This led us to hypothesize that there may be an involvement of Forkhead box protein, Foxm1 in regulating the cdk1 gene expression. This may be because SKP2 targets TIS21BTG2/PC3, an inhibitor of FoxM1 activation by inhibiting Cdk1 activity. TIS21BTG2/PC3 is recognized as a bona fide substrate of skp2. In this study, we would like to delineate the functionally relevant interaction which might exist between Foxm1 and Cdk1 at transcriptional and translational level. In depth understanding of the functional significance of Foxm1 and its interactome will provide better insights into the regulatory mechanisms involved in cell cycle. Thereby this study may pave the way for the identification of small molecules in targeted cancer therapy.

    Dhanya
    Dhanya

    Dhanya K, PhD Student

    Forkhead box (Fox) proteins are family of evolutionarily conserved transcriptional regulators, which control a wide spectrum of biological processes. A loss or gain of Forkhead proteins function can alter cell fate and promote tumorigenesis as well as cancer progression. Foxm1 is known to regulate the genes important for G1/S-transition, S-phase progression, G2/M transition and progression through M-phase. Abnormal up regulation of FoxM1 has been reported in majority of solid human cancers including liver, breast, lung, prostate, cervix, colon, pancreas and brain.
    Previous studies from our lab reported that, increased expression of CDK1 occurred when SKP2, an E3 ubiquitin ligase was over expressed. This led us to hypothesize that there may be an involvement of Forkhead box protein, Foxm1 in regulating the cdk1 gene expression. This may be because SKP2 targets TIS21BTG2/PC3, an inhibitor of FoxM1 activation by inhibiting Cdk1 activity. TIS21BTG2/PC3 is recognized as a bona fide substrate of skp2. In this study, we would like to delineate the functionally relevant interaction which might exist between Foxm1 and Cdk1 at transcriptional and translational level. In depth understanding of the functional significance of Foxm1 and its interactome will provide better insights into the regulatory mechanisms involved in cell cycle. Thereby this study may pave the way for the identification of small molecules in targeted cancer therapy.

    Tapas Pradhan, PhD Student

    Tapas Pradhan, PhD Student

    Chandraprabha M G, Senior Research Fellow

    Drug discovery in the ubiquitin system is less exploited compared to that of protein kinases. Receptor tyrosine kinases have extracellular domains that can also be targeted with therapeutic antibodies. But, the human genome encodes more E3 ubiquitin ligases than protein kinases. Furthermore, the E3 ligase confers specificity to ubiquitination when it transfers ubiquitin from an E2 to a particular substrate. For these reasons, E3 ubiquitin ligases are attractive candidates as drug targets. Given the diverse approaches and avenues that remain unexplored in developing drugs targeted at the ubiquitin system, this study could contribute in overcoming the barriers for the ubiquitin drug discovery. Transcription factor profiling is also a useful tool to investigate the pathogenesis of cancers. These transcription factors contribute to a malignant phenotype by regulating genes involved in cellular proliferation, survival, differentiation, angiogenesis, and invasion. STAT proteins are among the best-studied of these transcription factors, and are involved in oncogenesis both in vivo and in vitro. They thus represent an ideal model for understanding how transcription factors cause cancer through coordinated changes in gene expression. STAT3 is linked to inflammation-associated tumorigenesis that is initiated by genetic alterations in malignant cells, as well as by many environmental factors, including chemical carcinogens, infection, cigarette smoking and stress. The mechanism of how STAT3 is initially activated and remains persistently activated in cancer is still vague. Our study will help in addressing that question with the help of the hypothesis; that Stat3 activation leads to tumor cell cycle progression, at least through protein degradation of p27 by induction of Skp2 expression. Interestingly, significant level of Stat3 expression is predominantly found in colorectal cancer cases. Ultimately, this may provide the rationale for the development of therapeutics involving Stat3 inhibitors in combination with proteasome inhibitors against colon cancer-(molecular enhancing or synergizing). This study aims at a proteomic based expression analysis to comprehensively identify STAT target genes in the ubiquitin pathway. Analysis of these targets can provide insight into mechanisms of neoplastic transformation.

    chandra
    chandra

    Chandraprabha M G, Senior Research Fellow

    Drug discovery in the ubiquitin system is less exploited compared to that of protein kinases. Receptor tyrosine kinases have extracellular domains that can also be targeted with therapeutic antibodies. But, the human genome encodes more E3 ubiquitin ligases than protein kinases. Furthermore, the E3 ligase confers specificity to ubiquitination when it transfers ubiquitin from an E2 to a particular substrate. For these reasons, E3 ubiquitin ligases are attractive candidates as drug targets. Given the diverse approaches and avenues that remain unexplored in developing drugs targeted at the ubiquitin system, this study could contribute in overcoming the barriers for the ubiquitin drug discovery. Transcription factor profiling is also a useful tool to investigate the pathogenesis of cancers. These transcription factors contribute to a malignant phenotype by regulating genes involved in cellular proliferation, survival, differentiation, angiogenesis, and invasion. STAT proteins are among the best-studied of these transcription factors, and are involved in oncogenesis both in vivo and in vitro. They thus represent an ideal model for understanding how transcription factors cause cancer through coordinated changes in gene expression. STAT3 is linked to inflammation-associated tumorigenesis that is initiated by genetic alterations in malignant cells, as well as by many environmental factors, including chemical carcinogens, infection, cigarette smoking and stress. The mechanism of how STAT3 is initially activated and remains persistently activated in cancer is still vague. Our study will help in addressing that question with the help of the hypothesis; that Stat3 activation leads to tumor cell cycle progression, at least through protein degradation of p27 by induction of Skp2 expression. Interestingly, significant level of Stat3 expression is predominantly found in colorectal cancer cases. Ultimately, this may provide the rationale for the development of therapeutics involving Stat3 inhibitors in combination with proteasome inhibitors against colon cancer-(molecular enhancing or synergizing). This study aims at a proteomic based expression analysis to comprehensively identify STAT target genes in the ubiquitin pathway. Analysis of these targets can provide insight into mechanisms of neoplastic transformation.

    Krishnanand Padmanabhan, Senior Research Fellow

    Colorectal Cancer a malignant disorder of Colon and Rectum is largely a preventable one with good prognosis, if detected at an early stage. Until few years the CRC incidence for Indian Population had been the lowest. However in recent times the incidence rate of CRC for Indian Population and several other South East Asian nations is on rise. Interestingly this rise in incidence rate also correlates with younger predisposition to CRC. Since this younger predisposition is highly relevant for Indian Population we specifically aim to explore the molecular basis behind origin and progression of CRC in Indian population. With this objective we are exploring the transcriptome and proteome changes that occurs during CRC progression. Using biopsy and surgical resection samples our aim is to uncover the molecular changes at different stages of CRC progression from a single individual. Since we understand tumour as a tissue with heterogeneous genetic background it would be highly pertinent to understand how specific mutations are selected during CRC progression and post-chemo radiotherapy regimens. To fulfil the above objective we have started NGS based analysis of Exome and Transcriptome. In parallel with NGS experiments we perform a LS-MS analysis on enriched cellular fractions (Cancer stem cells, differentiated epithelial cells, fibroblasts and endothelial cells) from CRC tumours. Data from these whole genome approach would allow us to better understand the molecular basis of CRC and design predictive cum prognostic biomarkers that could improve the overall disease free survival rate of CRC patients.

    DSCN5496
    DSCN5496

    Krishnanand Padmanabhan, Senior Research Fellow

    Colorectal Cancer a malignant disorder of Colon and Rectum is largely a preventable one with good prognosis, if detected at an early stage. Until few years the CRC incidence for Indian Population had been the lowest. However in recent times the incidence rate of CRC for Indian Population and several other South East Asian nations is on rise. Interestingly this rise in incidence rate also correlates with younger predisposition to CRC. Since this younger predisposition is highly relevant for Indian Population we specifically aim to explore the molecular basis behind origin and progression of CRC in Indian population. With this objective we are exploring the transcriptome and proteome changes that occurs during CRC progression. Using biopsy and surgical resection samples our aim is to uncover the molecular changes at different stages of CRC progression from a single individual. Since we understand tumour as a tissue with heterogeneous genetic background it would be highly pertinent to understand how specific mutations are selected during CRC progression and post-chemo radiotherapy regimens. To fulfil the above objective we have started NGS based analysis of Exome and Transcriptome. In parallel with NGS experiments we perform a LS-MS analysis on enriched cellular fractions (Cancer stem cells, differentiated epithelial cells, fibroblasts and endothelial cells) from CRC tumours. Data from these whole genome approach would allow us to better understand the molecular basis of CRC and design predictive cum prognostic biomarkers that could improve the overall disease free survival rate of CRC patients.

    Nisha Asok kumar, Junior Research Fellow

    Recurrence at secondary locations, often years after removal of the primary tumor, accounts for most of the mortality associated with solid tumors such as in colorectal cancers. Studies have suggested that metastasis, resistance to chemo- and radiotherapy, and eventual relapse have been attributed to a distinct tumor subpopulation known as cancer stem cells (CSCs), leading to failure in cancer therapy. Although over the last decade, the surgical techniques and chemotherapy has improved, the survival rate of the patients with colorectal caricinoma has not increased remarkably. One of the main reasons for the failure of treatment is drug resistance which limits the effectiveness of chemotherapies and thereby disease recurrence. Therapeutic targeting of CSC sub-populations therefore represents a novel opportunity to eradicate tumor-initiating, potentially drug-resistant cancer cell sub-populations.
    The main objective of my work is to generate an understanding about the molecular basis of multidrug resistance (MDR) in patient tissues at different stages of disease progression. This is being accomplished by identifying and isolating side population (SP) from various surgical margins of colon cancer patients. The sorted SP cells are evaluated for its self renewal and proliferation ability and compared with its Non-SP counter part. The protein isolated from the tissue samples are also used to profile the expression of various stem cell markers and drug resistant proteins. The expression of these molecules will also be studied at the transcriptional level. Also, the ability of the sorted SP cells from various surgical margins to induce tumor formation in vivo and its potential to bring about metastasis is also be studied using an orthotropic mouse model.

    IMG-20131004-WA0005
    IMG-20131004-WA0005

    Nisha Asok kumar, Junior Research Fellow

    Recurrence at secondary locations, often years after removal of the primary tumor, accounts for most of the mortality associated with solid tumors such as in colorectal cancers. Studies have suggested that metastasis, resistance to chemo- and radiotherapy, and eventual relapse have been attributed to a distinct tumor subpopulation known as cancer stem cells (CSCs), leading to failure in cancer therapy. Although over the last decade, the surgical techniques and chemotherapy has improved, the survival rate of the patients with colorectal caricinoma has not increased remarkably. One of the main reasons for the failure of treatment is drug resistance which limits the effectiveness of chemotherapies and thereby disease recurrence. Therapeutic targeting of CSC sub-populations therefore represents a novel opportunity to eradicate tumor-initiating, potentially drug-resistant cancer cell sub-populations.
    The main objective of my work is to generate an understanding about the molecular basis of multidrug resistance (MDR) in patient tissues at different stages of disease progression. This is being accomplished by identifying and isolating side population (SP) from various surgical margins of colon cancer patients. The sorted SP cells are evaluated for its self renewal and proliferation ability and compared with its Non-SP counter part. The protein isolated from the tissue samples are also used to profile the expression of various stem cell markers and drug resistant proteins. The expression of these molecules will also be studied at the transcriptional level. Also, the ability of the sorted SP cells from various surgical margins to induce tumor formation in vivo and its potential to bring about metastasis is also be studied using an orthotropic mouse model.

    Meera R Nair, Research Assistant

    Meera R Nair, Research Assistant

    Manu Prasad M, Project Assistant

    Manu Prasad M, Project Assistant

    Prameela Kumari T.K

    My work includes technical support to the laboratory. I help students in autoclaving and sterilizing glassware, prepare buffers for students, collect distilled water, reagents and other miscellaneous items from the store.

    Prameela
    Prameela

    Prameela Kumari T.K

    My work includes technical support to the laboratory. I help students in autoclaving and sterilizing glassware, prepare buffers for students, collect distilled water, reagents and other miscellaneous items from the store.

  • Alumni