Neuro-Oncology Program

Gliomas, the most common form of brain tumors of the adult CNS, originate from neuroepithelial tissue and are classified morphologically as astrocytic, oligodendroglial, ependymal, and choroid plexus tumors. Glioblastoma multiforme (grade IV astrocytoma; GBM) is one of the most aggressive forms of brain tumors and a primary area of focus for the Neurooncology Group at MSCTR.

Gliomas, originate from the neuro-epithelial tissue and are classified morphologically as astrocytic, oligodendroglial, ependymal and choroid plexus tumors. Glioblastoma multiforme (grade IV astrocytoma; GBM) is one of the most aggressive, invasive, and destructive malignancies and has attracted clinical attention globally. In addition to uncontrolled proliferation and diffuse tissue invasion, neuro-degeneration is another attribute and a hall mark of malignant gliomas, the mechanism of which is poorly understood. Thus, there may be several processes that may be common between gliomas and neuro-degenerative disorders.

The focus of the Neuro-oncology Group at MSCTR will be:

  • To continue the discovery effort of understanding these tumors and the dynamics of associated molecular patterns from a clinical perspective. Also to relate the findings to neuro-degenerative conditions.

  • To develop well defined strategies, using the data that is already available, for translation to diagnostic, prognostic or therapeutic applications.

We envision implementation of the two arms in parallel, through a multi-disciplinary team effort, involving basic scientists with expertise in high throughput technologies, cell biologists, clinicians and informaticians. Embedded in these efforts will be the mission of mentoring young clinicians and research scientists who will lead MSCTR both as independent scientists and as a well-coordinated team directed towards improved neuro oncology practices. This will ensure continued institutional efforts. Gliomas, particularly Glioblastoma, are one of the most targeted tumors in clinical oncology research globally. Hence, the center will aim for networking with other national and international clinical centers in our efforts to formulate pioneering treatment models for malignant Glioblastoma.

People

Dr. Ravi Sirdeshmukh, Ph.D.
ravisirdeshmukh@gmail.com

Dr. Ravi Sirdeshmukhholds a joint appointment as Principal Advisor, Neuro-oncology Research at MSCTR. His research interests span in the areas of protein and nucleic acid biochemistry and his earlier work included RNA processing, mRNA stability, structure-function relationship of ‘ribonucleases’ and their regulation. More recently his interests have been in the areas of Proteomics of gliomas – a major class of brain tumors and Head & Neck cancers. He has trained and mentored a number of young associates, Ph.D. students and post-doctoral fellows. At MSCTR, he is spearheading translational research programs in brain tumors.

Raksha A. Ganesh, MSc
Senior Research Fellow
raksha.ganesh@ms-mf.org

After obtaining her Masters degree in Genetics from University of Mysore, she joined Center for Cellular and Molecular Biology, Hyderabad as a Junior Research Fellow, where she worked primarily on Functional Genomics and Cancer drug discovery. Currently she is pursuing Ph.D. and is a recipient of Senior Research Fellowship from ICMR. Her work constitutes developing a draft pathway map of an orphan GPCR in Glioblastoma multiforme through experimental and bioinformatics approaches.

Chaithra.B.A, MSc
Lab Assistant
chaithra.ba@ms-mf.org

After obtaining her master degree in Applied Genetics from the University of Bangalore, she worked as an intern for one month in the Molecular Diagnostics lab at MSCTR and for two months in Reametrixpvt.ltd, where she gained proficiency in several molecular biology techniques.Currently, she is working as a Research Assistant in MSCTR. Her work primarily involves maintaining the tissue repository for the Neuro-Oncology team and detailed follow-up of patients.

Pranali Sonpatki, MSc
Senior Research Fellow

After obtaining a Masters Degree in Bioinformatics she worked as a Bioinformatics Analyst for KovidBioAnalytics, Pune, where she worked for various universities providing services like NGS analysis and algorithm development.  Currently she is working as a Senior Research Fellow and her work includes developing bioinformatics pipelinefor integrated multi-omic dataanalysis for the neuro-oncology group.

Manoj Kumar Gupta, MSc
Collaborator

After obtaining his M.Sc. degree in Biotechnology from Bangalore University, he worked as a Junior Research Fellow at Indian Institute of Science (IISc), Bangalore and later worked as a Senior Research Fellow at the Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad. He is a recipient of Senior Research Fellowship from CSIR, Government of India and is currently pursuing Ph.D. at Institute of Bioinformatics (IOB) under the supervision of Dr. Ravi Sirdeshmukh. He is currently involved in the identification of cancer biomarkers and potential therapeutic targets for gliomas using proteomic approaches.

Savita Jayaram, MSc
Collaborator

Savita Jayaram obtained her M.S. degree in Molecular Genetics from Georgia State University, Atlanta and M.Sc. degree in Biochemistry from Hyderabad Central University, India. She has extensive experience in data annotation, data mining and use of bioinformatics software and worked at Iconix Biosciences, California; Nuvelo Inc., California; Accelrys Inc. and Strand Life Sciences. She is currently pursuing Ph.D. at Institute of Bioinformatics (IOB) under the supervision of Dr. Ravi Sirdeshmukhand her focus is multi-omic data analysis, data integration and deciphering altered signaling events for biomarker insights in Glioblastoma.

Publications

  • Kim, M. S., Pinto, S. M., Getnet, D., …….Sirdeshmukh, R.,….. C. A., Gowda, H. and Pandey, A. (2014). A draft map of the human proteome. Nature. 509, 575-581.
  • Chaiyarit S, Singhto N, Chen YJ, Cheng CY, Chiangjong W, Kanlaya R, Lam H, Peerapen P, Sung TY, Tipthara P, Pandey A, Poon TC, Chen YJ, Sirdeshmukh R, Chung MC, Thongboonkerd V. (2014). Chromosome-Centric Human Proteome Project (C-HPP): Chromosome 12. J Proteome Res. May 15.
  • Gupta, M. K., Jayaram, S., Madugundu, A. K., Chavan, S., Advani, J., Pandey, A., Thongboonkerd, V., Sirdeshmukh, R. (2014). Chromosome-Centric Human Proteome Project: Deciphering Proteins Associated with Glioma and Neurodegenerative Disorders on Chromosome 12. Journal of Proteome Research. 2014 May 7
  • Polisetty, R. V., Gautam, P., Gupta, M. K., Sharma, R., Uppin, M. S., Challa, S., Ankathi, P., Purohit, A. K., Renu, D., Harsha, H. C., Pandey, A. and Sirdeshmukh, R. (2013). Heterogeneous nuclear ribonucleoproteins and their interactors are a major class of deregulated proteins in anaplastic astrocytoma – a Grade III malignant glioma. Journal of Proteome Research.
  • Gupta, M. K., Polisetty, R. V., Ramamoorthy, K., Tiwary, S., Kaur, N., Shiras, A. and Sirdeshmukh, R. (2013). Secretome analysis of Glioblastoma cell line – HNGC-2. Molecular BioSystems. 9, 1390-1400. PubMed
  • Mushahary, D., Gautam, P., Sundaram, C. S. and Sirdeshmukh, R. (2013). Expanded protein expression profile of human placenta using two-dimensional gel electrophoresis. Placenta. 34, 193-196. PubMed
  • Gautam, P., Nair, S. C., Gupta, M. K., Sharma, R., Polisetty, R. V., Uppin, M. S., Challa, S., Puligopu, A. K., Ankathi, P., Purohit, A. K., Chandak, G. R., Harsha, H. C. and Sirdeshmukh, R. (2012). Proteins with altered levels in plasma from glioblastoma patients as revealed by iTRAQ-based quantitative proteomic analysis. PLOS ONE. 7, e46153. PubMed
  • Polisetty, R. V., Gautam, P., Sharma, R., Harsha, H. C., Nair, S. C., Gupta, M. K., Uppin, M. S., Challa, S., Puligopu, A. K., Ankathi, P., Purohit, A. K., Chandak, G. R., Pandey, A. and Sirdeshmukh, R. (2012). LC-MS/MS Analysis of Differentially Expressed Glioblastoma Membrane Proteome Reveals Altered Calcium Signalling and other Protein Groups of Regulatory Functions. Molecular and Cellular Proteomics. 11, M111.013565. PubMed
  • Gautam, P., Upadhyay, S. K., Hassan, W., Madan, T., Sirdeshmukh, R., Sundaram, C. S., Gade, W. N., Basir, S. F., Singh, Y. and Sarma, P. U. Transcriptomic and proteomic profile of Aspergillus fumigatus on exposure to artemisinin. Mycopathologia. 2011. 172, 331-346. PubMed
  • Polisetty, R. V., Gupta, M. K., Nair, S. C., Ramamoorthy, K., Tiwary, S., Shiras, A., Chandak, G. R. and Sirdeshmukh, R. Glioblastoma cell secretome: analysis of three glioblastoma cell lines reveal 148 non-redundant proteins. Journal of Proteomics. 2011. 74, 1918-1925. PubMed
  • Peng, L., Kapp, E. A., …Sirdeshmukh, R., ….Rawson, P. and Jordan, T. W. The Asia Oceania Human Proteome Organisation Membrane Proteomics Initiative. Preparation and characterisation of the carbonate-washed membrane standard. Proteomics. 2010. 10, 4142-4148. PubMed
  • Govekar, R. B., D’Cruz, A. K., Alok, P., Agarwal, J., Dinshaw, K. A., Chinoy, R. F., Gadewal, N., Kannan, S., Sirdeshmukh, R., Sundaram, C. S., Malgundkar, S. A., Kane, S. V. and Zingde, S. M. Proteomic profiling of cancer of the gingivo-buccal complex: Identification of new differentially expressed markers. Proteomics – Clinical Applications. 2009. 3, 1451-1462. PubMed
  • Gautam, P., Shankar, J., Madan, T., Sirdeshmukh, R., Sundaram, C. S., Gade, W. N., Basir, S. F. and Sarma, P. U. Proteomic and transcriptomic analysis of Aspergillus fumigatus on exposure to amphotericin B. Antimicrobial Agents and Chemotherapy. 2008. 52, 4220-4227. PubMed
  • Sirdeshmukh, R. Proteomics in India: an overview. Molecular & Cellular Proteomics. 2008. 7, 1406-1407. PubMed Mathivanan, S., Ahmed, M., …..Sirdeshmukh, R., ….. Zurbig, P. and Pandey, A. Human Proteinpedia enables sharing of human protein data. Nature Biotechnology. 2008. 26, 164-167. PubMed
  • Shukla, S., Govekar, R. B., Sirdeshmukh, R., Sundaram, C. S., D’Cruz, A. K., Pathak, K. A., Kane, S. V. and Zingde, S. M. Tumor antigens eliciting autoantibody response in cancer of gingivo-buccal complex. Proteomics – Clinical Applications. 2007. 1, 1592-1604. PubMed
  • Suhasini, A. N. and Sirdeshmukh, R. Onconase action on tRNA(Lys3), the primer for HIV-1 reverse transcription. Biochemical and Biophysical Research Communications. 2007. 363, 304-309. PubMed
  • Gautam, P., Sundaram, C. S., Madan, T., Gade, W. N., Shah, A., Sirdeshmukh, R. and Sarma, P. U. Identification of novel allergens of Aspergillus fumigatus using immunoproteomics approach. Clinical and Experimental Allergy: Journal of the British Society for Allergy. 2007. 37, 1239-1249. PubMed
  • Sirdeshmukh, R., Santosh, V., Srikanth, A. (2006) Differential protein expression, protein profiles of human gliomas and clinical implications. Bio Arrays – from Basics to diagnostics, 1st Ed., pp. 145 – 69, Editor- Appasani, K. Humana Press, N.J., USA
  • Suhasini, A. N. and Sirdeshmukh, R. Transfer RNA cleavages by onconase reveal unusual cleavage sites. The Journal of Biological Chemistry. 2006. 281, 12201-12209. PubMed
  • Chumbalkar, V. C., Subhashini, C., Dhople, V. M., Sundaram, C. S., Jagannadham, M. V., Kumar, K. N., Srinivas, P. N., Mythili, R., Rao, M. K., Kulkarni, M. J., Hegde, S., Hegde, A. S., Samual, C., Santosh, V., Singh, L. and Sirdeshmukh, R. Differential protein expression in human gliomas and molecular insights. Proteomics. 2005. 5, 1167-1177. PubMed
  • Saxena, S. K., Sirdeshmukh, R., Ardelt, W., Mikulski, S. M., Shogen, K. and Youle, R. J. Entry into cells and selective degradation of tRNAs by a cytotoxic member of the RNase A family. The Journal of Biological Chemistry. 2002. 277, 15142-15146. PubMed
  • Murthy, B. S., De, L., Piccoli, R., D’Alessio, G. and Sirdeshmukh, R. Effects of protein RNase inhibitor and substrate on the quaternary structures of bovine seminal RNase. Biochemistry. 1996. 35, 3880-3885. PubMed
  • Tharun, S. and Sirdeshmukh, R. Specific endonucleolytic cleavages of mouse albumin mRNA and their modulation during liver development. Nucleic Acids Research. 1995. 23, 641-646. PubMed
  • Rao, K. S., Sirdeshmukh, R. and Gupta, P. D. Modulation of cytosolic RNase activity by endogenous RNase inhibitor in rat vaginal epithelial cells on estradiol administration. FEBS Letters. 1994. 343, 11-14. PubMed
  • Murthy, B. S. and Sirdeshmukh, R. Sensitivity of monomeric and dimeric forms of bovine seminal ribonuclease to human placental ribonuclease inhibitor. The Biochemical Journal. 1992. 281 ( Pt 2), 343-348. PubMed
  • Krych, M., Sirdeshmukh, R., Gourse, R. and Schlessinger, D. Processing of Escherichia coli 16S rRNA with bacteriophage lambda leader sequences. Journal of Bacteriology. 1987. 169, 5523-5529. PubMed
  • King, T. C., Sirdeshmukh, R. and Schlessinger, D. (1986). Nucleolytic processing of ribonucleic acid transcripts in procaryotes. Microbiological Reviews. 428-451. PubMed
  • Schlessinger, D., Thomas, J. R., Krych, M., Sirdeshmukh, R. and Little, R. D. Ribosomal RNA processing in Escherichia coli and cultured mammalian cells. Biochemical Society Transactions. 1986. 14, 811-813. PubMed
  • Sirdeshmukh, R. and Schlessinger, D. Why is processing of 23 S ribosomal RNA in Escherichia coli not obligate for its function? Journal of Molecular Biology. 1985. 186, 669-672. PubMed
  • Sirdeshmukh, R. and Schlessinger, D. Ordered processing of Escherichia coli 23S rRNA in vitro. Nucleic Acids Research. 1985. 13, 5041-5054. PubMed
  • Schlessinger, D., Bolla, R. I., Sirdeshmukh, R. and Thomas, J. R. Spacers and processing of large ribosomal RNAs in Escherichia coli and mouse cells. BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology. 1985. 3, 14-18. PubMed
  • Sirdeshmukh, R., Krych, M. and Schlessinger, D. Escherichia coli 23S ribosomal RNA truncated at its 5′ terminus. Nucleic Acids Research. 1985. 13, 1185-1192. PubMed
  • Sirdeshmukh, R., Vijayarangam, D. and Bhargava, P. M. E. coli RNA entrapped in large unilamellar liposomes is partially exposed. Indian Journal of Biochemistry & Biophysics. 1984. 21, 293-298. PubMed
  • King, T. C., Sirdeshmukh, R. and Schlessinger, D. RNase III cleavage is obligate for maturation but not for function of Escherichia coli pre-23S rRNA. Proceedings of the National Academy of Sciences of the United States of America. 1984. 81, 185-188. PubMed
  • Sirdeshmukh, R. B. and Bhargava, P. M. Uptake of exogenous RNA by rat-liver parenchymal cells in suspension prepared by the collagenase method. Indian Journal of Biochemistry & Biophysics. 1983. 20, 121-126. PubMed
  • Sirdeshmukh, R. and Bhargava, P. M. Evidence for the presence of a cell-surface ribonuclease in mechanically prepared rat-liver cells in suspension. Bioscience Reports. 1982. 2, 751-760. PubMed
  • 1. Polisetty RV, Gautam P, Gupta MK, Sharma R, Harsha HC, Renu D, Shivakumar BM, Lakshmikantha A, Mariswamappa K, Ankathi P, Purohit AK, Uppin MS, Challa S, Sirdeshmukh R. Microsomal Membrane proteome of low grade diffused astrocytomas: Differentially Expressed Proteins and candidate circulatory/ surveillance biomarkers. (Accepted in Scientific Reports)
  • 2. Sirdeshmukh R,Somasundaram K, Zingde SM. Cancer proteomics in India. Nature India. 2015doi:10.1038/nindia.2015.119.
  • 3. Sirdeshmukh R,Zingde SM, Dharmalingam K, Vijayalakshmi MA. Bench to bedside: Still a pipedream?Nature India. 2015doi:10.1038/nindia.2015.113.
  • 4. Sirdeshmukh R. (2016) India and the Quest Towards Human Proteome. J Proteins and Proteomics 7(1), MTT 1.
  • 5. Gupta MK, Jayaram S, Reddy DN, Polisetty RV, and Sirdeshmukh R.Transcriptomic and Proteomic data integration and 2D molecular maps with regulatory and functional linkages: Application to Cell Proliferation and Invasion Networks in Glioblastoma. J. Proteome Res., October 14, 2015, DOI:10.1021/acs.jproteome.5b00765
  • 6. Sivadasan P, Gupta MK, Sathe GJ, Balakrishnan L, Palit P, Gowda H, Suresh A, Kuriakose MA, Sirdeshmukh R. Human salivary proteome - a resource of potential biomarkers for oral cancer. J Proteomics. 2015 Sep 8;127(Pt A):89-95. doi: 10.1016/j.jprot.2015.05.039.
  • 7. Jayaram S, Gupta MK, Shivakumar BM, Ghatge M, Sharma A, Vangala RK, Sirdeshmukh R. Insights from Chromosome-Centric Mapping of Disease-Associated Genes: Chromosome 12 Perspective. J Proteome Res. 2015 Sep 4;14(9):3432-40.
  • 8. Sivadasan P, Gupta MK, Sathe GJ, Balakrishnan L, Palit P, Gowda H, Suresh A, Kuriakose MA, Sirdeshmukh R. Data from human salivary proteome - A resource of potential biomarkers for oral cancer. Data Brief. 2015 Jul 2;4:374-8. doi: 10.1016/j.dib.2015.06.014.
  • 9. Sirdeshmukh R. Indian proteomics efforts and human proteome project. J Proteomics. 2015 Sep 8;127(Pt A):147-51. doi: 10.1016/j.jprot.2015.03.018.
  • 10. Jayaram S, Gupta MK, Polisetty RV, Cho WC, Sirdeshmukh R. Towards developing biomarkers for glioblastoma multiforme: a proteomics view. Expert Rev Proteomics. 2014 Oct;11(5):621-39.
  • 11. Manda SS, Nirujogi RS, Pinto SM, Kim MS, Datta KK, Sirdeshmukh R, Prasad TS, Thongboonkerd V, Pandey A, Gowda H. (2014). Identification and Characterization of Proteins Encoded by Chromosome 12 as Part of Chromosome-centric Human Proteome Project. J Proteome Res. 13(7):3166-77.
  • 1. Gautam P, Mushahary D, Hassan W, Upadhyay SK, Madan T, Sirdeshmukh R,Sundaram CS, Sarma PU. In-depth 2-DE reference map of Aspergillus fumigatus and its proteomic profiling on exposure to itraconazole. Med Mycol. 2016 Feb 11. pii: myv122.
  • 2. Pawar H, Srikanth SM, Kashyap MK, Sathe G, Chavan S, Singal M, Manju HC, Kumar KV, Vijayakumar M, Sirdeshmukh R, Pandey A, Prasad TS, Gowda H, Kumar RV. Downregulation of S100 Calcium Binding Protein A9 in Esophageal Squamous Cell Carcinoma. ScientificWorldJournal. 2015;2015:325721. doi: 10.1155/2015/325721.
  • 3. Daswani B, Gupta MK, Gavali S, Desai M, Sathe GJ, Patil A, Parte P, Sirdeshmukh R, Khatkhatay MI. Monocyte Proteomics Reveals Involvement of Phosphorylated HSP27 in the Pathogenesis of Osteoporosis. Dis Markers. 2015;2015:196589. doi: 10.1155/2015/196589.
  • 4. Kelkar DS, Provost E, Chaerkady R, Muthusamy B, Manda SS, Subbannayya T, Selvan LD, Wang CH, Datta KK, Woo S, Dwivedi SB, Renuse S, Getnet D, Huang TC, Kim MS, Pinto SM, Mitchell CJ, Madugundu AK, Kumar P, Sharma J, Advani J, Dey G, Balakrishnan L, Syed N, Nanjappa V, Subbannayya Y, Goel R, Prasad TS, Bafna V, Sirdeshmukh R, Gowda H, Wang C, Leach SD, Pandey A. Annotation of the zebrafish genome through an integrated transcriptomic and proteomic analysis. Mol Cell Proteomics. 2014 Nov;13(11):3184-98. doi: 10.1074/mcp.M114.038299
  • 5. Thomas JK, Kim MS, Balakrishnan L, Nanjappa V, Raju R, Marimuthu A, Radhakrishnan A, Muthusamy B, Khan AA, Sakamuri S, Tankala SG, Singal M, Nair B, Sirdeshmukh R, Chatterjee A, Prasad TS, Maitra A, Gowda H, Hruban RH, Pandey A. (2014). Pancreatic Cancer Database: An integrative resource for pancreatic cancer. Cancer BiolTher. 15(8).
  • 6. Nanjappa V, Thomas JK, Marimuthu A, Muthusamy B, Radhakrishnan A, Sharma R, Ahmad Khan A, Balakrishnan L, Sahasrabuddhe NA, Kumar S, Jhaveri BN, Sheth KV, Kumar Khatana R, Shaw PG, Srikanth SM, Mathur PP, Shankar S, Nagaraja D, Christopher R, Mathivanan S, Raju R, Sirdeshmukh R, Chatterjee A, Simpson RJ, Harsha HC, Pandey A, Prasad TS. (2014) Plasma Proteome Database as a resource for proteomics research: 2014 update. Nucleic Acids Res. 42(1):D959-65
  • 7. Mahajan L, Pandit H, Madan T, Gautam P, Yadav AK, Warke H, Sundaram CS, Sirdeshmukh R, Sarma PU, Kishore U, Surolia A. Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line. PLoS One. 2013 Dec 31;8(12):e85046. doi: 10.1371/journal.pone.0085046.