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Dr. Padma Shastry

Scientist 'G'
National Centre for Cell Science
NCCS Complex, Pune University Campus
Ganeshkhind, PUNE- 411 007, INDIA
Ph.: +91-020-25708108, 25708000
Fax: +91-020-25692259
E-mail:  

 

Profile | Research Activities | Selected Publications | Collaborators | Fundings | Lab Members

 

 

Profile

 

Dr. Padma Shastry is a senior scientist (Scientist G) in National Centre for Cell science (NCCS), Pune. She is PhD from Bombay University, India and did her post- doctoral studies at University of Alberta, Edmonton, Canada. She joined the Immunology department of CVTC, KEM hospital, Parel, Bombay in 1984 as a pool officer and continued as Senior Scientific Officer and worked in the area of Immunology of Acute rheumatic fever and rheumatic heart disease. Since 1990, she is working at National Centre for Cell Science (NCCS earlier NFATCC). She has developed in vitro system using cell lines as alternatives to animals for assessing antibodies to tetanus. Her research interests are in cancer biology and currently the projects are focused on understanding studying drug resistance/ sensitivity in gliomas using different experimental models, elucidating the signal transduction pathways in proliferation, survival and invasion in gliomas for identification of molecules for drug targets.

The group employs multidisciplinary approaches including different in-vitro experimental models, cell biology techniques in development of cell lines form tumors and knock down using siRNA and targeted antisense oligonucleotides  to study-

  • Mechanisms of drug resistance and sensitivity in gliomas using monolayers (2D) and multicellular spheroids (MCS) cultured cells

  • The role of Akt/PKB – NF-kappaB signaling in proliferation in survival, proliferation and invasion in gliomas

  • To decipher the mechanisms of tumor environment with emphasis on inflammatory cytokines in modulation of mTORC2 complex signaling in tumor progression.

Her research interests also include -stem cell biology and fungal lectins in cancer biology.

 

 

 

 

Research Activities

 

 

GOWRY DAS G, UGC-SRF  gowry

 

Understanding invasion in Gliomas through Signaling

Glioblastoma multiforme (GBM) is the highly aggressive and most common primary brain tumor in adults with a dismal survival of one year post diagnosis. Malignant gliomas display extensive infiltration into the surrounding brain tissue making them resistant to the existing therapeutic strategies. Monocytes are recruited to the primary tumor site where they differentiate into tumor associated macrophages (TAMs) and secrete inflammatory cytokines such as Tumor Necrosis Factor-a (TNF-a), Interleukin-1b (IL-1b), VEGF and other chemokines that positively regulate invasion and angiogenesis aided by the secretion of high levels of proteolytic enzymes such as Matrix Metalloproteinases (MMPs).
Our team is involved in the study of TNF-a-mediated signal transduction pathways that control the aggressive nature of gliomas in terms of resistance to various drugs and ability to invade other sites in the brain. The pathways of interest are those that involve PI3K/Akt, mTOR and NF-kB and their downstream targets. Apart from the two-dimensional glioma cell cultures, the group has developed three-dimensional multi-cellular spheroids that mimic the in vivo tumor cell architecture better. We also extend our experiments using primary cultures derived from brain samples of GBM patients undergoing surgery. The other area of interest is the effect of the tumor microenvironment in the progression of gliomas. We have consistently proved that cytokines in the vicinity of the tumor affect the tumor’s growth which is detrimental to the host. These cytokines are powerful modulators of tumor resistance and it is important to include strategies in cancer therapy that do not just eliminate cancer cells but target the microenvironment which continuously supports the tumor growth and invasion.

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The expression of Matrix metalloproteinase – 9 (MMP-9) in glioma cell line – LN18, is shown in green, along with staining of Actin filaments in red.

 

 

 

 

 

RADHA PUJARI, ICMR-SRF  radha

 

 

Delineating cellular signaling induced by Rhizoctonia bataticola lectin (RBL) in normal human PBMC and leukemic cells

A novel lectin has been isolated and characterized from phytopathogenic fungus, Rhizoctonia bataticola, by Dr. B.M. Swamy and his group at the Department of Biochemistry, Karnatak University, Dharwad.  Rhizoctonia bataticola lectin (RBL) was isolated from the fungal mycelium. Glycan array analysis revealed high affinity binding of RBL towards N-glycans and glycoproteins containing complex N-glycan chains. We studied the binding and biological response of RBL in normal human peripheral blood mononuclear cells. Our findings revealed, RBL is highly mitogenic towards human peripheral blood mononuclear cells and possess immunostimulatory activity. It induces the secretion of various Th1 and Th2 cytokines such as IL-2, IFNg, IL-12, IL-10 and IL-4. To elucidate the intracellular signaling cascade evoked by RBL, Mitogen Activated Protein Kinase(MAPK) and the Signal Transducers and Activators of Transcription (STAT) pathway was studied. Our findings implicated p38 MAPK and STAT pathway in RBL mediated proliferation, IL-2Rα (CD25) expression and production of cytokines.
RBL exhibited binding to human T-cell leukemia cell lines-Molt-4 and Jurkat. The study of its biological activity revealed that RBL induces apoptosis in these cell lines. Thus RBL acts as double-edged sword wherein on one hand it stimulates immune response and on the other it induces cytotoxicity in cancer cells without affecting the normal cells.

It is one of the aims of natural complementary medical therapy to stimulate natural resistance in order to restrain cancer progression or improve defective immunological conditions. RBL due to its unique sugar recognition properties and differential response in normal and cancer cells can be probed for its therapeutic potential in cancer management.

 

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MRUTHYUNJAYA S, DBT-SRF  MJ

 

 

Stem Cell Biology-Understanding mechanisms in laminin-1-induced neurite outgrowth in human bone marrow mesenchymal stem cells.

 

Human bone marrow mesenchymal stem cells (MSCs) are of clinical interest in cell based therapies for the treatment of neurodegenerative diseases. Efforts are therefore directed towards efficient generation of neuron-like cells from MSCs. A multitude of growth and differentiation factors have been employed for driving MSCs towards a neuronal phenotype. In our laboratory, we investigated  the potential of extracellular matrix (ECM) proteins-fibronectin, collagen-1, collagen-IV, laminin-1 and laminin-10/11, to induce neurite outgrowth/ differentiation in bone marrow derived human MSCs in the absence of  any growth factors/differentiating agents. Our findings showed that direct interaction with laminin-1 triggered sprouting of neuritic processes. Integrin function-blocking studies confirmed the involvement of integrin a6b1 in neurite outgrowth. Mechanistic studies revealed FAK, MEK and ERK pathways were involved in laminin-1-stimulated neurite formation. Further studies are focused to investigate the roles of immediate early genes of AP-1 family (c-Jun, c-fos) and proneural genes (neuroD1 and neurogenin-1) in neurite formation. As multiple signaling pathways are involved in a biological response such as neurite outgrowth, we are also studying the activation of signaling proteins such as Src, JNK and Akt during neuritogenesis. Attempts are underway to understand the cross-talks between the signaling pathways that play crucial roles in neurite formation

 

 

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Fibronectin staining

CD90 expression             

Neurites on laminin-1

 

 

 

 

 

Publications

 

  1. Rictor regulates MMP-9 activity and invasion through Raf-1-MEK-ERK signaling pathway in glioma cells. Das G, Shiras A, Shanmuganandam K, Shastry P. Mol Carcinog. 2010 Dec 28.

  2. Rhizoctonia bataticola lectin (RBL) induces mitogenesis and cytokine production in human PBMC via p38 MAPK and STAT-5 signaling pathways. Pujari R, Nagre NN, Chachadi VB, Inamdar SR, Swamy BM, Shastry P.  Biochim Biophys Acta. 2010 Dec;1800(12):1268-75.

  3. A potent mitogenic lectin from the mycelia of a phytopathogenic fungus, Rhizoctonia bataticola, with complex sugar specificity and cytotoxic effect on human ovarian cancer cells. Nagre NN, Chachadi VB, Sundaram PM, Naik RS, Pujari R, Shastry P, Swamy BM, Inamdar SR. Glycoconj J. 2010 Apr;27(3):375-86.

  4. Laminin-1 induces neurite outgrowth in human mesenchymal stem cells in  serum/differentiation factors-free conditions through activation of FAK-MEK/ERK signaling pathways. Mruthyunjaya S, Manchanda R, Godbole R, Pujari R, Shiras A, Shastry P.Biochem Biophys Res Commun. 2010 Jan 1;391(1):43-8. Epub 2009 Nov 4.

  5. Differential expression and role of p21cip/waf1 and p27kip1 in TNF alpha induced inhibition of proliferation in human glioma cells.. Sudheer Kumar P, Shiras A, Das G, Jagtap JC, Prasad V, Shastry P  : Mol Cancer. 2007 Jun 12;6(1):42

  6. Independent activation of Akt and NF-kappaB pathways and their role in   resistance to TNF-alpha mediated cytotoxicity in gliomas. Sudheer Kumar P, Anjali Shiras, Gowry Das, Jayashree C Jagtap, Vandna Prasad and  Padma Shastry. Mol Carcinog. 2008 Feb;47(2):126-36.

  7. Spontaneous transformation of human adult non-tumorigenic stem cells to cancer stem cells is driven by Genomic instability in a human model of glioblastoma. Anjali Shiras, Sivarajan Chettiar T, Varsha Shepal, G. Rajendra Prasad, Ganeshkumar Rajendran,  Padma Shastry .  Stem Cells. 2007 Jun;25(6):1478-89.

  8. ROS-triggered caspase 2 activation and feedback amplification loop in beta-carotene-induced apoptosis Prasad V, Chandele A, Jagtap JC, Sudheer Kumar P, Shastry PFree Radic Biol Med. 2006 Aug 1;41(3):431-42.

  9. A commentary  -- β-Carotene: A colorful killer of cancer cells ? Free Radic Biol  Med 41(3):431-42.2006 . A commentary  -- β-Carotene: A colorful killer of cancer cells ? was published highlighting the findings by Prasad et al in paper “ROS-triggered caspase 2 activation and feedback amplification loop in β-carotene-induced apoptosis” ( Free Radic Biol Med Aug 1;41(3):431-42.2006 ).The article commented on the novel mechanistic evidence involving the importance of  role of caspase-2 and feedback/cross talk among  caspases -2, -3, -8, in the killing of a human T-lymphoblast leukemia cell line (MOLT-4) by β-carotene.

  10. Upregulation of survivin in G2/M cells and inhibition of caspase 9 activity enhances resistance in staurosporine-induced apoptosis . Chandele A, Prasad.V , Jagtap. J, Shukla.R , Shastry.P . Neoplasia. 2004, Vol 6,(1) 29-40

  11. Modulation of cytokine profiles by malaria pigment--hemozoin: role of IL-10 in suppression of proliferative responses of mitogen stimulated human PBMC.  Deshpande P, Shastry PCytokine. 2004 Dec 21;28(6):205-13

  12. A Unique Model System for Tumor Progression in GBM Comprising Two Developed Human Neuro-Epithelial Cell Lines with Differential Transforming Potential and Co-expressing Neuronal and Glial. Shiras A ; Bhosale.A ; Shepal. V ; Shukla. R ; Baburao V ; Prabhakara K.; Shastry P.   Neoplasia, 2003,  Vol.5 (6) 520 – 532

  13. Sodium pyruvate protects against H2O2  mediated apoptosis in human neuroblastoma cell. Jayashree C. Jagtap, Anmol Chandele   A .Chopde  Padma Shastry  J Chem Neuroanat. 2003 Oct;26(2):109-18

  14. Differential expression  of CD44 standard and variant isoforms in two dimensional and three dimensional  cultured from B16F10 melanoma cell line. Anjali Shiras,  Arti Bhosale Anjali Patekar, Varsha Shepal and Padma Shastry Clin.Exp.Metastasis.2002;19(5):445-55.

  15. Monocyte –macrophage differentiation invitro: modulation by extracellular matrix protein substratum.. Shiney Susan Jacob, Padma Shastry and PR Sudhakaran Mol.Cell.Biochem..2002. 233(1-2):9-17.

 

 

 

Collaborators

 

Dr. Rumma Manchanda and Dr Ravibhusan Gokhale ( Stem cell project)
KEM Hospital, Pune.

Prof. B.M Swami and Prof. Shashikala Inamdar (Fungal lectins in cancer)
Biochemistry Dept., Karnataka Univ. Dharwad

Dr. Deepak Ranade, Neurosurgeon, Pune ( Gliomas and Chemoresistance)

Dr. Anjali Shiras, NCCS, Pune. (In- house collaborator)- Glioma and Stem cell biology

Jayashree Jagtap  (Technician)

 

 

 

Fundings

  • Role of Prostrate Apoptosis Response-4 (Par-4 )and its interactive proteins in chemo resistance/ sensitivity in gliomas using multi-cellular spheroids (MCS) as  model. ICMR 2010-2013 

  • Exploring the potential of Tf antigen binding property of lectin from sclerotium rolfsii for anticancer effect.   DBT- 2010-2013

  • Differentiation of human Mesenchymal stem cells (MSC)  towards  neuronal  lineages.   DBT – 2005-2008

  • Gene expression profiles during  neuronal differentiation and survival induced by lithium. BRNS ( Board of Radiation and Nuclear Studies )- 2005-2008

  • TF antigen binding unique lectins from Sclerotium rolfsii and Rhizoctonia bataticola for investigating aberrant glycosylation and changes associated with cancer- DST 2005-2008

  • MultiCellular spheroids (MCS) - A 3D  invitro  model  for studies  on  Cellular Molecular aspects  of  tumor progression and metastasis   ICMR  2002-2005.

 

 

Lab Members

 

Our Team

We believe in- We the TEAM and not I the Player

 

Present Working Team 

Gowry Das G (UGC- SRF)-  2005-

Mruthyunjaya S (DBT-SRF)-2005-

Radha Pujari (ICMR-SRF) – 2005-

Natesh Kumar (CSIR-JRF)- 2009-

G.N.V.R Chandrika ( CSIR-JRF)- 2011-

Ms. Jayashree C Jagtap (Technical officer A)

Ms. Reecha Shah-  Research Assistant  (ICMR- Project)

Ms Parveen Dawood (project trainee)- Jan. -May  2011

Our Ex- team members

Dr Sonia Gawande (DBT-PDF)- (2008-2010)

Dr Sudheer Kumar –awarded PhD in 2007

Dr  Vandna Prasad - awarded PhD in 2007

Dr Anmol Chandele- awarded PhD in 2004

Dr Nagratna. R         - awarded PhD in 2000

Ganesh Shelke – Project trainee- 2009- 2010

 

 

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NCCS Complex,University of Pune Campus,Ganeshkhind,Pune 411007,Maharashtra,India Phone: +91-20-25708000 Fax:+91-20-25692259 Gram:ATCELL