Profile

Research

Publications

Team

Alumni

S Sreeja, PhD

Scientist E-II

+91-471-2529474

ssreeja@rgcb.res.in

sreeja
  • Profile

    • Ph.D Biotechnology (University of Kerala)
    • till date - Scientist EII, Rajiv Gandhi Centre for Biotechnology
    • IACR, SBTI
  • Research

    Current Area of Research

    Our laboratory is interested in the signaling pathways involved in estrogen and progesterone action in hormone driven cancers. Estrogen hormones exhibit a broad spectrum of physiological functions but abnormally high estrogen levels are associated with the increased incidence of certain endocrine related cancers. Role of Progesterone, another important, yet understudied hormone remains controversial in breast cancer. The major biological actions of these hormones, estrogen and progesterone are mediated by their respective receptors, estrogen receptor (α/β) and progesterone receptor (PR). Progesterone receptors are also known to be regulated by estrogen receptor α . The mode of action of these hormones involves non-genomic pathways, genomic and often a cross talk of both. There are intricate signaling pathways that regulate the mechanism of these hormones and often interlinked. We are interested in understanding these complex mechanisms and signaling pathway involved .

    Specific areas of Research :

    • Estrogen Signaling in thyroid cancer
    • Biphasic action of progesterone in breast cancer
    • Molecular mechanism of 27-hydroxycholesterol as SERM
    • PhytoSERMS
  • Publications

    1. S Sreeja, T R Santhosh Kumar, S Lakshmi,Sreeja S*. 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, 23 (2012) 725-732
    2. Jazir Haneef, Parvathy M, Santhoshkumar R Thankayyan, Hima Sithul, Sreeja S* Bax Translocation Mediated Mitochondrial Apoptosis and Caspase Dependent Photosensitizing Effect of Ficus religiosa on Cancer Cells, PLoSONE 7(7): e40055. doi:10.1371/journal.pone.0040055;  (2012 )
    3. Sreeja S, Hima Sithul, Parvathy Muraleedharan, Juberiya Mohammed Azeez, Sreeja S*, "Pomegranate Fruit as a Rich Source of Biologically Active Compounds", BioMed Research Internationa l  Volume   (2014),    http://dx.doi.org/10.1155/2014/686921.
    4. Juberiya M. Azeez#, Hima Sithul, Indhu Hariharan, Sreeja Sreekumar, Jem Prabhakar, S.Sreeja*  and M. Radhakrishna Pillai ,"Progesterone regulates the proliferation of breast cancer cells -  invitro evidence", Drug design, Development and Therapy Vol:9,5987-5999,http://dx.doi.org/10.2147/DDDT. .S89390  (2015)
    5. Hima sithul and S.Sreeja* "Regulatory role of Estrogen induced Reactive Oxygen Species in the modulatory function of UCP 2 in Papillary Thyroid Cancer cells",  IUBMB Life DOI 10.1002/iub.1440   (2015)
    6. Vini Ravindran #, Juberiya M Azeez # and  S.Sreeja* Evidence of  pomegranate methanolic extract (PME) for antagonizing the endogenous SERM, 27- Hydroxycholesterol, International Union of Biochemistry and Molecular Biology,   DOI: 10.1002/iub.1465 (2015)
    7. Parvathy Muraleedharan#, Sreeja S#, Rakesh Kumar, Madhavan Radhakrishna Pillai*. P21 Activated Kinase 1 (PAK1) and its substrates as potential therapeutic targets in oral cancer. BMC CANCER (Accepted ) (2015.)
    8. Hima sithul and S.Sreeja* Modulatory effect of Estrogen in Tumor Micro Environment of Papillary Thyroid Carcinoma, IUBMB Life  DOI 10.1002/iub.1462  (2015)
    9. Ravindran Vini and S.Sreeja*,Punica granatum and its therapeutic implications on breast carcinogenesis: A review. BioFactors 04/; 41(2).DOI;10.1002/ biof.1206  (2015)
  • Team


    Jazir Haneef, PhD Student

    Molecular effects of flavonoids on Estrogen Receptor (ER) mediated pathways

    The steroid hormone estrogen causes its multitude effects through estrogen receptors that mediate the transcription of number of genes involved in reproduction, metabolism, growth and differentiation. It has been widely established that flavonoids, a group of polyphenolic phytochemicals can exert various biological effects including anti-oxidant, anti-carcinogenic, anti-inflammatory and also modulate the function of sex hormones and their receptors. Experimental studies have also revealed that these components regulate the molecules in the cell signaling transduction pathways, including NF-?B, MAPK, p53, AR and ER pathways. In this study I am focusing on finding out flavonoids with potential estrogenic activities, elucidating the molecular mechanisms of action of individual phytoestrogens and its use against hormone dependant cancers giving emphasis to estrogen receptor mediated pathways.

    jazir
    jazir

    Jazir Haneef, PhD Student

    Molecular effects of flavonoids on Estrogen Receptor (ER) mediated pathways

    The steroid hormone estrogen causes its multitude effects through estrogen receptors that mediate the transcription of number of genes involved in reproduction, metabolism, growth and differentiation. It has been widely established that flavonoids, a group of polyphenolic phytochemicals can exert various biological effects including anti-oxidant, anti-carcinogenic, anti-inflammatory and also modulate the function of sex hormones and their receptors. Experimental studies have also revealed that these components regulate the molecules in the cell signaling transduction pathways, including NF-?B, MAPK, p53, AR and ER pathways. In this study I am focusing on finding out flavonoids with potential estrogenic activities, elucidating the molecular mechanisms of action of individual phytoestrogens and its use against hormone dependant cancers giving emphasis to estrogen receptor mediated pathways.

    Parvathy M, PhD Student

    FUNCTIONAL ROLE OF P21 ACTIVATED KINASES (PAKs) IN ORAL CANCER*

    According to GLOBOCAN report of 2008, Oral Cancer is the second most common cancer among men in India. Despite considerable advances in treatment modalities, overall prognosis for patients with OSCC has not improved in the past two decades. This calls for the identification of new target molecules and translating them to clinical settings. A potential set of such target molecules is P21 Activated Kinases or PAKs, a family of serine/threonine kinases with roles in cell survival and oncogenesis. PAKs have been shown to play important role in the progression of cancer types like that of breast, ovarian etc by interfering in important cellular functions like cytoskeletal remodelling, cell cycle progression, angiogenesis, mitosis etc. However, its role and significance in Oral Cancer remains poorly understood. The focus of the on-going studies is to understand the role of PAKs in Oral Cancer progression.
    * Collaborative work with George Washington University

    parvathy1
    parvathy1

    Parvathy M, PhD Student

    FUNCTIONAL ROLE OF P21 ACTIVATED KINASES (PAKs) IN ORAL CANCER*

    According to GLOBOCAN report of 2008, Oral Cancer is the second most common cancer among men in India. Despite considerable advances in treatment modalities, overall prognosis for patients with OSCC has not improved in the past two decades. This calls for the identification of new target molecules and translating them to clinical settings. A potential set of such target molecules is P21 Activated Kinases or PAKs, a family of serine/threonine kinases with roles in cell survival and oncogenesis. PAKs have been shown to play important role in the progression of cancer types like that of breast, ovarian etc by interfering in important cellular functions like cytoskeletal remodelling, cell cycle progression, angiogenesis, mitosis etc. However, its role and significance in Oral Cancer remains poorly understood. The focus of the on-going studies is to understand the role of PAKs in Oral Cancer progression.
    * Collaborative work with George Washington University

    Lakshmi M L, PhD Student

    Regulatory role of Estrogen and Ezrin in the invasion of Papillary Thyroid Cancer cells

    Incidence of thyroid carcinoma is the most common endocrine malignancy, more prevalent in females than in males. This sex bias in incidence highlights the possible involvement of estrogen in proliferation, migration and invasion of thyroid carcinoma. Incidence of thyroid carcinoma is observed to be increased with the onset of puberty and decreasing after menopause. I am interested in looking at the role of estrogen in modulating cyotoskeletal proteins like ezrin, which belongs to Ezrin/ Radixin/ Moesin (ERM) family since it is an integral element in tumor metastasis and is over expressed in many aggressive carcinomas. Ezrin is known to regulate the actin reorganization by cross-linking actin filaments with plasma membrane. My aim is to investigate the role of estrogen in modulating ezrin and associated signaling proteins.

    lakshmi
    lakshmi

    Lakshmi M L, PhD Student

    Regulatory role of Estrogen and Ezrin in the invasion of Papillary Thyroid Cancer cells

    Incidence of thyroid carcinoma is the most common endocrine malignancy, more prevalent in females than in males. This sex bias in incidence highlights the possible involvement of estrogen in proliferation, migration and invasion of thyroid carcinoma. Incidence of thyroid carcinoma is observed to be increased with the onset of puberty and decreasing after menopause. I am interested in looking at the role of estrogen in modulating cyotoskeletal proteins like ezrin, which belongs to Ezrin/ Radixin/ Moesin (ERM) family since it is an integral element in tumor metastasis and is over expressed in many aggressive carcinomas. Ezrin is known to regulate the actin reorganization by cross-linking actin filaments with plasma membrane. My aim is to investigate the role of estrogen in modulating ezrin and associated signaling proteins.

    Hima Sithul, Research Fellow

    Modulatory role of UCP2 (Uncoupling protein 2) in thyroid cancer

    Thyroid cancer (TC) is an endocrine related cancer and is well coupled with the female reproductive hormone, 17-β-estradiol (estrogen).Clear mechanism of estrogen and its role in thyroid cancer is not yet known. Our earlier findings demonstrated that estrogen regulates reactive oxygen species and mitochondrial potential wherein modulation of UCP2 seemed one of the mechanisms. We aim to further understand the molecular mechanism involved in estrogen mediated thyroid cancer progression.

    hima
    hima

    Hima Sithul, Research Fellow

    Modulatory role of UCP2 (Uncoupling protein 2) in thyroid cancer

    Thyroid cancer (TC) is an endocrine related cancer and is well coupled with the female reproductive hormone, 17-β-estradiol (estrogen).Clear mechanism of estrogen and its role in thyroid cancer is not yet known. Our earlier findings demonstrated that estrogen regulates reactive oxygen species and mitochondrial potential wherein modulation of UCP2 seemed one of the mechanisms. We aim to further understand the molecular mechanism involved in estrogen mediated thyroid cancer progression.

    Juberiya M Azeez, PhD student

    Progesterone and breast cancer

    Progesterone is reported to have a biphasic action on breast cancer that is either stimulate breast tumor growth or suppress proliferation. The action of progesterone has been found to be time depended. I am interested in the molecular mechanisms governing these events .Our earlier research has demonstrate the role of reactive oxygen in modulating action of progesterone. We further aim to find the specific role of progesterone receptor, its isoforms and relevance to the biphasic action in breast cancer.

    juberia
    juberia

    Juberiya M Azeez, PhD student

    Progesterone and breast cancer

    Progesterone is reported to have a biphasic action on breast cancer that is either stimulate breast tumor growth or suppress proliferation. The action of progesterone has been found to be time depended. I am interested in the molecular mechanisms governing these events .Our earlier research has demonstrate the role of reactive oxygen in modulating action of progesterone. We further aim to find the specific role of progesterone receptor, its isoforms and relevance to the biphasic action in breast cancer.

    Vini Ravindran, PhD student

    Obesity, 27-hydroxycholesterol and breast cancer

    Cholesterol is a known risk factor for breast cancer. Recent discovery of 27-hydroxycholesterol, an oxysterol as an endogenous selective estrogen modulators (SERM), and its adverse effects in breast cancer via estrogen receptor has provided a new insight into pathology of cholesterol linked breast cancer. In essence, 27HC possess all the deleterious effects of estrogen in the hormone dependent tissues and none if its benefits. What intrigues us is the molecular mechanism of 27HC and how similar or different is the molecule from estrogen , in terms of its molecular targets. Also, our recent research on of SERM activity of pomegranate methanolic extract led us to hypothesize that this could serve to compete with 27HC and plausibly reduce its deleterious effects. We are in quest for finding the active compound which could be a phytoSERM and can potentially compete with 27HC and antagonize its action.

    vinii
    vinii

    Vini Ravindran, PhD student

    Obesity, 27-hydroxycholesterol and breast cancer

    Cholesterol is a known risk factor for breast cancer. Recent discovery of 27-hydroxycholesterol, an oxysterol as an endogenous selective estrogen modulators (SERM), and its adverse effects in breast cancer via estrogen receptor has provided a new insight into pathology of cholesterol linked breast cancer. In essence, 27HC possess all the deleterious effects of estrogen in the hormone dependent tissues and none if its benefits. What intrigues us is the molecular mechanism of 27HC and how similar or different is the molecule from estrogen , in terms of its molecular targets. Also, our recent research on of SERM activity of pomegranate methanolic extract led us to hypothesize that this could serve to compete with 27HC and plausibly reduce its deleterious effects. We are in quest for finding the active compound which could be a phytoSERM and can potentially compete with 27HC and antagonize its action.

  • Alumni


    Sreeja Sreekumar, PhD

    Post-doctoral Associate
    Oesterreich Lab
    Womens Cancer Research Centre
    University of Pittsburgh

    Sreeja Sreekumar
    Sreeja Sreekumar

    Sreeja Sreekumar, PhD

    Post-doctoral Associate
    Oesterreich Lab
    Womens Cancer Research Centre
    University of Pittsburgh