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Radhika Nair, PhD

Ramanujan Faculty Fellow

+91-471-2781251

radhikanair@rgcb.res.in

radhikanair
radhikanair

Radhika Nair, PhD

Ramanujan Faculty Fellow

+91-471-2781251

radhikanair@rgcb.res.in

  • Profile

    • PhD, National Institute of Immunology, New Delhi, India
    • M.Sc., Biochemistry, Institute of Science, Bombay, India
    • B.Sc. Honours, St.Xavier's College,Bombay,India
    • Ramanujan Faculty Fellow, Rajiv Gandhi Centre for Biotechnology
    • Conjoint lecturer, Faculty of Medicine, St Vincent's Clinical School
    • Senior Research Officer, Cancer Research Program, The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Australia
    • Career Development Fellow, University of Cambridge, UK
    • Ramanujan fellowship (awarded by Department of Science and Technology, India)
    • Career development fellowship (awarded by the Medical Research Council) at the MRC-Hutchison Cancer Cell Unit, Cambridge, UK
    • Senior Research Fellowship by DBT, Government of India
    • Junior Research Fellowship by DBT, Government of India
    • Bombay University merit based scholarship for M.Sc.
    • VSRP programme at TIFR, Bombay (India)
    • American Association for the Advancement of Science
    • Metastasis Research Society (MRS)
  • Research

    Metastasis or the spread of cancer from the primary site to other parts of the body is a silent killer in breast cancer, with 80% mortality rate for women with metastatic disease. Key questions that need to be dealt with include heterogeneity and a detailed understanding of the cells critical for actual metastatic establishment. Therapeutic targeting of metastasis requires a deeper understanding of the metastatic process and our work will directly address key challenges in the field.

    Hypothesis

    Comprehending the cell intrinsic mechanisms that allow a tumour cell to survive, remain in a state of dormancy and then thrive in a hostile new environment of a distant metastatic organ is vital. In addition, analyzing the role of the extracellular environment in supporting metastatic cells is key to giving us a complete picture of the metastatic process. The hypothesis underpinning the work in my laboratory is that breast cancer cells form metastases utilizing a combination of cell autonomous ('intrinsic') programs and microenvironmental ('extrinsic') changes. This work has implications for conceptually understanding the critical molecules involved in the metastatic process and identifying its "Achilles' heel", which can be exploited for therapeutic purposes.


    In vivo imaging of 4T1 breast cancer cells in mouse models.
    Metastatic dissemination imaged in the brain and lungs.

    Project 1- Defining the molecular mechanisms of metastasis

    The main aim of this work is to delineate the key molecular players involved in the cell autonomous control of metastatic cells. We will use a 'pipeline' of technologies to make fundamental discoveries in breast cancer molecular etiology, and then test their relevance in sophisticated in vitro and in vivo models and human disease. Two key skills will involve the use of Patient Derived Xenografts to model the complexity of human metastatic disease and Single Cell technology (Gene expression, RNA Sequencing) to understand the molecular networks that underpin these rare cell populations.


    Image of tumoursphere formed by a highly aggressive breast cancer model generated in mice. The cells are stained for DNA (Blue,DAPI) and a putative metastasis promoting factor (Red).

    Project 2- Deconvoluting the tumour- metastatic niche microenvironment

    The importance of the microenvironment in cancer progression and metastasis is being increasingly recognized. A critical component is to establish the identity of the metastasis associated stromal (MAS) cell required for the establishment of the metastatic niche. This will be further leveraged to identify molecular pathways in the extracellular environment critical for the establishment of dormancy and metastasis.


    Use of Single Cell technology to understand the underlying molecular networks of rare populations in a highly metastatic breast cancer cell line.

    • ECR grant, SERB (DST), 2016- 2019
    • Ramanujan Fellowship, Department of Science and Technology, 2015- 2020
  • Publications

    1. Junankar S, Baker LA, Roden DL, Nair R, Elsworth B, Gallego-Ortega D, Lacaze P, Cazet A, Nikolic I, Teo WS, Yang J, McFarland A, Harvey K, Naylor MJ, Lakhani SR, Simpson PT, Raghavendra A, Saunus J, Madore J, Kaplan W, Ormandy C, Millar EK, O’Toole S, Yun K, Swarbrick A. ID4 controls mammary stem cells and marks breast cancer with a stem cell-like phenotype. March 2015 Nature Communications
    2. Phua YW, Nguyen A, Roden D, Elsworth B, Deng N, Nikolic I, Yang J, Mcfarland A, Russell R, Kaplan W, Cowley M, Nair R, Zotenko E, O’Toole S, Tan SX, James DE, Clark SJ, Kouros-Mehr H, Swarbrick A. MicroRNA profiling of the developing mouse mammary gland identifies miR-184 as a candidate breast tumour suppressor gene. May 2015 Breast Cancer Research
    3. Teo SW, Nair R, Swarbrick A. New insights into the role of ID proteins in breast cancer metastasis: a MET affair. May 2014 Breast Cancer Research
    4. Nair R*, Teo SW*, Mittal V, Swarbrick A. ID proteins regulate diverse aspects of cancer progression and provide novel therapeutic oppurtunities. (* co-first authors). May 2014 Molecular Therapy
    5. PimentelB*-Nair R*, Bermejo-Rodriguez C, Agu C, Preston M, Wang X,Bernal JA, Sherrat D and de la Cueva-Mendez G. Toxin Kid uncouples DNA replication and cell division to enforce retention of plasmid R1 in E.coli cells . (*co-first authors). Jan 21 2014; Proceedings of the National Academy of Sciences
    6. Nair R, Roden D, Teo WS, McFarland A, Junankar S , Ye S, Nguyen A, Yang J , Nikolic I, Morey A, Shah J, Selinger C, Baker LA, Cowley M, Naylor MJ, Ormandy CJ,  Lakhani SR, Kaplan W, O’Toole SA, Swarbrick, A. A Myc transcriptional program that is independent of EMT drives a poor prognosis tumour- propagating phenotype in HER2+ breast cancer. Sep 23 2013, Oncogene  
    7. Ali NA, Wu J, Hochgräfe F, Chan H, Nair R, Ye S, Zhang L, Lyons RJ, Pinese M, Lee HC, Armstrong N, Ormandy CJ, Clark SJ, Swarbrick A, Daly RJ. Profiling the tyrosine phosphoproteome of mouse mammary tumor models reveals distinct signaling networks and conserved oncogenic pathways. September 2014, Breast Cancer Research
    8. Karlo Dante T. Natividad; Simon Rajesh Junankar; Norhanani Mohd Redzwan; Radhika Nair; Rushika Christina Wirasinha; Cecile King; Robert Brink; Alexander Swarbrick; Marcel Batten. Interleukin-27 signaling promotes immunity against endogenously arising murine tumors. 2013
    9. Mun Hui, Aurélie Cazet, Radhika Nair, D Neil Watkins, Sandra A. O’Toole  and Alexander Swarbrick. The Hedgehog Signalling Pathway in Breast Development, Carcinogenesis and Cancer Therapy. 2013, Mar 28;15(2):203 Breast Cancer Research 
    10. O’Toole, S.A., Machalek, D., Shearer, R., Millar, E.A., Nair, R., McLeod, D., Cooper, C., McFarland, A., Qiu, M., McNeil, C.M., Rabinovich, B., Martelotto, L., Vu, D., Sutherland, R.L., Watkins, N., and Swarbrick, A. (2011). Hedgehog ligand overexpression predicts poor outcome and is a potential therapeutic target for metastatic disease. 2011 Jun 1;71(11):4002-4014 Cancer Research
    11. Hochgräfe, F., Zhang, L., O’Toole, S., Browne, B.C., Pinese, M., Porta Cubas, A., Lehrbach, G.M., Croucher, D.R., Rickwood, D., Boulghourjian, A., Shearer, R., Nair, R., Swarbrick, A., Biankin, A.V., Sutherland, R.L., J., R.M., and Daly, R.J. (2010). Tyrosine phosphorylation profiling reveals the signaling network characteristics of basal breast cancer cells. 2010 Nov 15;70(22):9391-401 Cancer Research
    12. Nair, R., Junankar, S., O’Toole, S., Shah, J., Borowsky, A.D., Bishop, J.M., and Swarbrick, A. Redefining the expression and function of the inhibitor of differentiation 1 in mammary gland development. 2010 PLoS ONE
    13. Nair R, Shaha C.Diethylstilbestrol induces rat spermatogenic cell apoptosis in vivo through increased expression of spermatogenic cell Fas/FasL system.Vol. 278, Issue 8, 6470-6481, February 21, 2003, J. Biol. Chem.
  • Team


    Reshma Murali, Project Assistant (DST grant)

    Deciphering the molecular circuitry of Cancer Stem Cells

    Breast cancer is the most common type of cancer among women and has a significant health burden in India. Patient prognosis depends on the tumor subtype and impacts on therapeutic strategy. We have made rapid progress in the treatment of the ER+ and Her2+ subtypes of breast cancer. Unfortunately due to lack of expression of ER, HER2 and PR, we currently have no targeted therapy available for the Triple Negative Breast Cancer (TNBC) subtype. There also exists highly diverse intra-tumoural heterogeneity, with a subpopulation of tumour cells (termed Cancer Stem Cells/ CSCs) driving critical cancer phenotypes such as metastasis, self-renewal and chemoresistance. Effective therapeutic targeting of CSCs is essential for the complete eradication of a tumour and prevention of relapse in patients due to outgrowth of chemoresistant CSCs. Transcription factors are critical regulators of normal cellular differentiation and lineage commitment. The Inhibitor of Differentiation (ID) proteins are helix-loop-helix transcriptional repressors with established roles in stem cell self renewal, lineage commitment and niche interactions. Recent studies have demonstrated that Id1 is over expressed in the poor prognosis TNBC subtype, controls proliferation and is required for breast cancer cells to escape oncogene induced cellular senescence. Our hypothesis is that Id1 marks CSCs in a proportion of TNBCs, enabling us to prospectively isolate and dissect the biology controlling the phenotype of this unique subpopulation of cells. This will also helps us in the identification and analysis of pathways critical to CSC survival.

    Syed Khaja Mohieddin
    Syed Khaja Mohieddin

    Reshma Murali, Project Assistant (DST grant)

    Deciphering the molecular circuitry of Cancer Stem Cells

    Breast cancer is the most common type of cancer among women and has a significant health burden in India. Patient prognosis depends on the tumor subtype and impacts on therapeutic strategy. We have made rapid progress in the treatment of the ER+ and Her2+ subtypes of breast cancer. Unfortunately due to lack of expression of ER, HER2 and PR, we currently have no targeted therapy available for the Triple Negative Breast Cancer (TNBC) subtype. There also exists highly diverse intra-tumoural heterogeneity, with a subpopulation of tumour cells (termed Cancer Stem Cells/ CSCs) driving critical cancer phenotypes such as metastasis, self-renewal and chemoresistance. Effective therapeutic targeting of CSCs is essential for the complete eradication of a tumour and prevention of relapse in patients due to outgrowth of chemoresistant CSCs. Transcription factors are critical regulators of normal cellular differentiation and lineage commitment. The Inhibitor of Differentiation (ID) proteins are helix-loop-helix transcriptional repressors with established roles in stem cell self renewal, lineage commitment and niche interactions. Recent studies have demonstrated that Id1 is over expressed in the poor prognosis TNBC subtype, controls proliferation and is required for breast cancer cells to escape oncogene induced cellular senescence. Our hypothesis is that Id1 marks CSCs in a proportion of TNBCs, enabling us to prospectively isolate and dissect the biology controlling the phenotype of this unique subpopulation of cells. This will also helps us in the identification and analysis of pathways critical to CSC survival.

    Binitha Anu Varghese, Project Assistant (DST grant)

    Deciphering Breast Cancer Metastasis

    Research over the last two decades has seen the emergence of targeted therapies, which along with systemic therapies (such as chemotherapy and hormonal therapies) has revolutionized the management of breast cancer. However, there is currently no targeted therapy for metastatic disease which accounts for 90% of total mortality rate. Metastasis or the spread of cancer from the primary site to other parts of the body is a highly complex process involving a series of molecular events. Therapeutic targeting of metastasis thus requires a deeper understanding of the metastatic process. My work deals with understanding the key molecular pathways that are critical for establishment of metastasis in the organs like the lung and liver.

    Binitha
    Binitha

    Binitha Anu Varghese, Project Assistant (DST grant)

    Deciphering Breast Cancer Metastasis

    Research over the last two decades has seen the emergence of targeted therapies, which along with systemic therapies (such as chemotherapy and hormonal therapies) has revolutionized the management of breast cancer. However, there is currently no targeted therapy for metastatic disease which accounts for 90% of total mortality rate. Metastasis or the spread of cancer from the primary site to other parts of the body is a highly complex process involving a series of molecular events. Therapeutic targeting of metastasis thus requires a deeper understanding of the metastatic process. My work deals with understanding the key molecular pathways that are critical for establishment of metastasis in the organs like the lung and liver.

  • Alumni