Dr. Padma Shastry
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.
GOWRY DAS G, UGC-SRF
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.
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
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.
MRUTHYUNJAYA S, DBT-SRF
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
Neurites on laminin-1
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)
We believe in- We the TEAM and not I the Player
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
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