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A S Sreedhar

Senior Principal Scientist

Research Interests

Heat Shock Proteins in Biology and Medicine: Our group is working on stress response and heat shock proteins (Hsps) in biology and medicine. We are studying the molecular basis of stress response and transcriptional regulation of Hsp synthesis during development, differentiation and stress management to identify the unconventional roles of heat shock transcription factors in tumor cells. High expression of Hsps, especially the Hsp90 in tumor cells correlates with poor prognosis and accelerated disease progression. Therefore we are studying effect of Hsp90 inhibition in anticancer treatments and elucidating novel functions of Hsps. Inducing cytostasis or apoptosis in tumor cells may induce unwanted cellular response. We are evaluating stress (physiological or oncogene), or Hsp inhibition or over expression induced cellular senescence as a tumor suppressor mechanism. Our group is also involved in molecular targeting of cancer using natural compounds, and evaluation of combinatorial treatments as beneficial tool for cancer

Selected Publications

Shrikant PD, Paithankar K, Abhijnya KV, Hatim SK, Sreedhar AS
Mitochondrial chaperone, TRAP1 modulates mitochondrial dynamics and promotes tumor metastasis
Mitochondrion. doi: https://doi.org/10.1016/j.mito.2020.08.001

Vijayalakshmi A, Khanderao P, Shrikanth PD, Abirami A, Sreedhar AS.
Development of Nanocarrier-Based Mitochondrial Chaperone, TRAP-1 Inhibitor to Combat Cancer Metabolism.
ACS Appl. Bio Mater. 2020, 3, 7, 4188–4197. https://doi.org/10.1021/acsabm.0c00268

Ramkumar B, Dharaskar SP, Mounika G, Paithankar K, Sreedhar AS.
Mitochondrial chaperone, TRAP1 as a potential pharmacological target to combat cancer metabolism.
Mitochondrion. 2020;50:42-50. doi:10.1016/j.mito.2019.09.011

Kumar P, Devaki B, Jonnala UK, Sreedhar AS.
Hsp90 facilitates acquired drug resistance of tumor cells through cholesterol modulation however independent of tumor progression.
Biochim Biophys Acta Mol Cell Res. 2020;1867(8):118728. doi:10.1016/j.bbamcr.2020.118728

Kanugovi AV, Joseph C, Siripini S, Paithankar K, Sreedhar AS.
Compromising the constitutive p16INK4a expression sensitizes human neuroblastoma cells to Hsp90 inhibition and promotes premature senescence.
J Cell Biochem. 2020;121(4):2770-2781. doi:10.1002/jcb.29493

Vykuntham NG, Suran S, Siripini S, John S, Kumar P, Paithankar K, Sreedhar AS. (2020).
Altered molecular pathways decides the treatment outcome of Hsp90 inhibitors against breast cancer cells.
Toxicology in vitro : an international journal published in association with BIBRA, 65, 104828. https://doi.org/10.1016/j.tiv.2020.104828

Education & Experiance

P.G: Biochemistry ; SV University ; 1991-92
Ph.D: Hsp90 inhibitors: their effects on redox status and on the cytosrchitecture ; Semmelweis University, Hungary ; 2004
Post.Doc:

Stress Biology ; Kyoto University, Japan ; 2007

Experience:

NIL

Publications

TitleJournalYear
Mitochondrial chaperone, TRAP1 modulates mitochondrial dynamics and promotes tumor metastasis Mitochondrion, doi: https://doi.org/10.1016/j.mito.2020.08.001 2020
Development of nanocarrier-based mitochondrial chaperone, TRAP-1 inhibitor to combat cancer metabolism. ACS Appl. Bio Mater. (doi: https://dx.doi.org/10.1021/acsabm.0c00268.) 2020
The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis Cancer Reports : doi:10.1002/cnr2.1261 2020
Altered molecular pathways decides the treatment outcome of Hsp90 inhibitors against breast cancer cells Toxicology in Vitro, 2020 https://doi.org/10.1016/j.tiv.2020.104828 2020
Hsp90 facilitates acquired drug resistance of tumor cells through cholesterol modulation however independent of tumor progression Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, https://doi.org/10.1016/j.bbamcr.2020.118728 2020
Mitochondrial chaperone, TRAP1 as a potential pharmacological target to combat cancer metabolism. Mitochondrion. 2019 Oct 25. pii: S1567-7249(19)30019-4. doi: 10.1016/j.mito.2019.09.011. 2019
Compromising the constitutive p16(INK4a) expression sensitizes human neuroblastoma cells to Hsp90 inhibition and promotes premature senescence. J Cell Biochem. 2019 Nov 6. doi:10.1002/jcb.29493. 2019
The tumor suppressor p16INK4a expression bypasses 17AAG mediated cellular effects in human neuroblastoma, IMR-32 Transl Med, Vol 6, p 74. 2016,doi: 10.4172/2161-1025.c.1.020 2016
The prosurvival activity of HSF2 in response to autophagic stress is triggered by HSF2 - dependent transactivation of BTG2 Mol Biol Cell, 26(25): 4523,doi: 10.1091/mbc.E15-09-0674 2015
Molecular characterization and expression analysis of hsp60 gene homologue of sheep blowfly, Lucilia cuprina J Therm Biol, Vol 52, p 24-37.,doi: 10.1016/j.jtherbio.2015.05.001. 2015
Oncogene de-addiction from Hsp90 induces senescence-like phenotype in malignant and metastatic tumor cells Mol Biol Cell, vol. 25, p 25 3987,doi:10.1091/mbc.E14-10-1437 2014
Synthesis, anticancer and antibacterial activities of piplartine derivatives on cell cycle regulation and growth inhibition Journal of Asian Natural Products Research. 15:658-669, 2013. 2013
Cipadessin-type limonoids from the leaves of Cipadessa baccifera Tetrahedron Letters, 54: 2934-2937, 2013. 2013
Geldanamycin combination with colcemid induces mitotic arrest through stabilization of bubR1 mitotic kinase in human tumor cells Journal of Cancer Therapy, 4: 709-719, 2013 2013
Hsp60 chaperonin acts as barrier to pharmacologically induced oxidative stress mediated apoptosis in tumor cells with differential stress response Drug Target Insights, Vol 7, p 35-51 doi: 10.4137/DTI.S12513 2013
17AAG treatment accelerates doxorubicin induced cellular senescence: Hsp90 interferes with enforced senescence of tumor cells Drug Target Insights,6:19-39 2012
Glutamete carboxypeptidase II (GCPII) genetic variants as determinants of hyperhomocysteinemia: Implications in stroke susceptibility Indian J Biochem & Biophys, 49:356-362, 2012. 2012
Heat shock proteins in the cancer immunity: comprehensive review on potential chemotherapeutic interventions J. Clin. Cell. Immunol. 6: 1-8, 2012. 2012
Association of Glutamate Carboxypeptidase II (GCPII) Haplotypes with Breast and Prostate Cancer Risk Gene, 516: 76-81, 2012. 2012
Repercussion of mitochondria structural deformity induced by anti-Hsp90 drug 17AAG in human tumor cells Journal of Drug Target Insights, 5: 1-22,2011 2011
Anti-microbial principles of selected remedial plants from southern India Asian Pacific J Tropical Biomedicine,1: 298-305, 2011 2011
Pharmacological inhibition of Hsp90 as a novel antitumor strategy to target cytoarchitecture through extracellular matrix signaling. Medicinal Chemistry,7:1-12, 2011 2011
Synthesis and anticancer effects of pongamol derivatives on mitogen signaling and cell cycle kinases Medicinal Chemistry Reserach, Published online on 30-Jan-2011 2011
Combinatorial effect of 17AAG and doxorubicin on stress induced cellular senescence of human neuroblastoma cells J. Ind. Acad. Geriatrics. 6: 133, 2010. 2010
Hsp90 inhibition induces destabilization of actin cytoskeleton in tumor cells: functional significance of Hsp90 interaction with F-actin. Asian Pacfic Journal of Tropical Medicine, Vol. 3, 715-722 2010
17-(Allylamino)-17-demethoxygeldanamycin combination with diferuloylmethane selectively targets mitogen kinase pathway in a human neuroblastoma cell line Journal of Cancer Therapy, Vol. 1,197-204. 2010
p53 pseudogene: potential role in heat shock induced apoptosis in a rat histiocytoma HEALTH, Vol.2, 1065-1071. 2010
Hsp70 confines tumor progression of rat histiocytoma and impedes the cytotoxicity induced by natural killer cells and peritoneal macrophages Asia Pacific J. Trop. Med., Vol. 3 (4): 302-309. 2010
Stress proteins in biology and medicine: evolution, adaptation and clinical evaluation. Int. J. Pharma & Biosci. Vol. 1(3): 1-35, 2010. 2010
Hsp90 inhibitors, GA and 17AAG, leads to ER-stress induced apoptosis in rat histiocytoma. Biochem. Pharmacol. 78: 141-152 2009
Diferuloylmethane augments the cytotoxic effects of piplartine isolated from Piper chaba. Toxicology in Vitro. Vol.23: 1085-1091 2009
Stress response and emerging roles of heat shock proteins: Bench to Bedside. Icfai J. Bitechnol 2: 31-50 2008
Heat shock transcription factors in the regulation of stress induced cell death pathways in a rat histiocytoma J. Biosci., 32: 585-593 2007
Heat shock transcription factors: a comprohensive review. In stress response: a molecular biology approach (Eds. A. S. Sreedhar and Usha K. Srinivas) ISBN: 81-308-0109-4, Research Signpost. 2006
Heat shock proteins in the clinical and pharmacological perspective. In stress response: a molecular biology approach (Eds. A. S. Sreedhar and Usha K. Srinivas) ISBN: 81-308-0109-4, Research Signpost. 2006
Stress response: a molecular biology approach ISBN: 81-308-0109-4, Research Signpost. 2006
Hyperthermia and pharmacological interventions of heat shock proteins in anticancer treatments Japanese Journal of Hyperthermic Oncology, 22(4): 201-227 2006
Effect of unfolded protein accumulation on the redox state of the endoplasmic reticulum. In: Redox regulation (eds: A. Pompella, G. Banhegyi and M. Wellman-Rousseau), NATO Science Series, 363: 111-119 2005
Hidden dimensions of stress response Everyman`s Science, XL: 179-185 2005
Effect of Hsp90 inhibitors, geldanamycin, 17-allylamino-17-demethoxygeldanamycin and curcumin on human neuroblastoma cells, IMR-32. FEBS J., 272(s1): G1-008P 2005
Heat Shock Proteins in the regulation of apoptosis: New strategies in tumor therapy Pharmacol. & Ther., 101: 227-257 2004
Inhibition of Hsp90: a new strategy for inhibiting protein kinases Biochim. Biophys. Acta (Proteins and Proteomics)., 1697: 233-242 2004
Enhancement of complement-induced cell lysis. A novel mechanism for the anticancer effects of Hsp90 inhibitors Immunol. Lett., 92: 157-161 2004
Hsp90 isoforms: functions, expression and clinical importance FEBS Letts., 562: 11-15 2004
Effect of potassium application on growth attributes and stem histology of chickpea grown in vertisol Nat. J. Life Sci., 1: 187-191 2004
Apoptosis, necrosis and cellular senescence: chaperone occupancy as a potential switch Aging Cell, 2: 39-45 2003
Novel Roles of Hsp90 inhibitors and Hsp90 in: redox regulation and cytoarchitecture Rec. Res. Develop. Life Sci., 1: 153-171 2003
Hsp90 inhibition accelerates cell lysis: anti-Hsp90 ribozyme reveals a complex mechanism of Hsp90 inhibitors involving both superoxide- and Hsp90-dependent events J. Biol. Chem., 278: 35231-35240 2003
Interaction of neuropeptide Y and Hsp90 through a novel peptide-binding region Biochemistry (US), 42: 12972-12980 2003
Molecular chaperones, evolution and in medicine J. Mol. Struct. (THEOCHEM), 666-667: 373-380 2003
A cross talk between cell signalling and cellular redox state during heat induced apoptosis in a rat histiocytoma Free Radic. Biol. Med., 32: 221-227 2002
Effect of C-terminal deletion of p53 on heat induced CD95 expression and apoptosis in a rat histiocytoma Oncogene, 21: 4042-4049 2002
Activation of stress response by ionomycin in rat hepatoma cells. J. Cell. Biochem., 86: 154-161 2002
Emerging role for Hsp90 in protein folding, evolution, cell organization, and aging Eur. J. Biochem., 269: 3.3-5 2002
Role of stress response proteins in the regulation of cell death process Cell Stress and Chaperones , 5: 338-338 2001
Heat induced expression of CD95 and its correlation with the activation of apoptosis upon heat shock in rat histiocytic tumor cells FEBS Letts., 472: 271-275 2000

A S Sreedhar

Senior Principal Scientist

2698

assr@ccmb.res.in

A Vijaya Lakshmi

Senior Principal Scientist

2555

viji@cccmb.res.in

K R Paithankar

Principal Tech. Officer

2610

krp@ccmb.res.in

Akhil Kotwal

Senior Research Fellow

2610

akhil@ccmb.res.in

Pankaj Kumar

Senior Research Fellow

2610

Shrikant Dharaskar

Junior Research Fellow

2610