Assessment of radiation resistance and therapeutic targeting of cancer stem cells: A Raman spectroscopic study of brain cancer (Kumar et al., 2018 Analytical Chemistry 90; 12067
A five lncRNA risk score predicted survival independent of all other markers in GBM Paul et al., 2018 Oncotarget 9;29548
Identification of 13-CpG methylation signature to distinguish IDH1 mutant GBM from IDH WT GBM Paul et al., 2017 Clinical Epigenetics 9; 32
Assessment of radiation resistance and therapeutic targeting of cancer stem cells: A Raman spectroscopic study of brain cancer (Kumar et al., 2018 Analytical Chemistry 90; 12067
Cancer Biology and Epigenetics
Cancer development is a complex process involving the accumulation of genetic alteration in genes that normally regulate cell proliferation, differentiation and death. In the laboratory, my research team is seeking to understand the molecular mechanisms underlying the development of central nervous system tumors, in particular gliomas which are tumors arising from glial cells. The grade IV glioma (Glioblastoma; GBM) is the most common, malignant primary brain tumor in adults. The prognosis remains poor with median survival ranging from 12-17 months in spite of improvements in treatment protocol. While our primary aim is to understand the biology of glioma, we also develop biomarkers/signatures for better grading, prognosis and treatment.
Some specific aspects of study focus on miRNA, DNA methylation and chromatin modifications. We also use next generation sequencing to identify novel genetic alterations and gene fusions in gliomas.
Research
The major emphasis is to understand the biology of cancer. Cancer can be defined in simple terms as an abnormal of cell growth with potential to invade other parts of the organ where it arises and also to other organs of the body. We investigate the genetic and epigenetic changes that are occurring during cancer development. More specifically, we concentrate on glioma, the tumor of glial cells, is the most common primary adult brain tumor. Glioblastoma, the grade IV glioma, is most aggressive type. Despite advances in the biology and therapeutic modalities, the prognosis remains poor. Genetic and epigenetic changes are characteristic of all cancers. We follow a comprehensive approach that integrates the changes in the genome and the epigenome of the cancer. While the genomic changes are unraveled by whole exome sequencing, the alterations in the cancer epigenome are revealed by analyzing DNA methylation, chromatin modifications, mRNA modifications and studying the regulation of noncoding RNAs. Two important recent findings are described below.
Graphical representation of the mechanism of action of Calcitonin/CALCR axis in glioma. The panel on
the left describestherapeutic utilization of CT-CALCR axis in CALCR WT glioma. The panel on the right
describes how CALCR mutation abolishes CT-CALCR tumor suppressor pathway leading to an aggressive
GBM tumor.
In an effort to gain a better understanding of the world around us, we have recently begun to use a new technique to investigate the organization and functionality of the diverse parts of our experimental model. We are currently looking to expand this work by collaborating with other labs who have the facilities and prior experience to investigate this project further.
METTL3 imparts stemness and radioresistance in GBM GSCs show elevated expression of METTL3 compared to DGCs and
the METTL3 levels further increases with gamma-irradiation. In GSCs, METTL3 methylates SOX2 mRNA. The methylation recruits
HuR to the modified SOX2 and stabilizes the mRNA which enhances the stem-like properties. In irradiated GSCs, further enhanced
expression of METTL3 leads to additional induction of SOX2 transcripts which support the radioresistant nature of GSCs.
In another project related glioma stem-like cells (GSC), we investigated the role of mRNA modification as an epigenetic regulation. N6-methyl adenosine, one of the abundant mRNA modifications catalyzed by methyltransferase-like 3 and 14 (METTL3/14), influences various events in RNA metabolism. We identified that m6A modification is higher in GSCs and METTL3-dependent m6A modification is crucial for GSC maintenance. We identified SOX2 as one of down-stream targets and further recruitment of HuR onto m6A modified sites in SOX2 mRNA leads to SOX2 mRNA stabilization. Additional studies revealed METTL3 enhances the DNA repair efficiency and radiation sensitivity partially via SOX2 in GSCs (see below). Thus we report the involvement of METTL3 in GSC maintenance and it might serve as a better target to overcome stem-like phenotype and radio resistance in GSC (Visvanathan et al., 2018).
Grants
Indian Council of Medical Research (ICMR)
Department of Biotechnology (DBT)
The Wellcome Trust, UK is greatly appreciated
People
Prof. Kumaravel Somasundaram
BVSc., Ph.D. (Madurai Kamaraj University)
​
PhD Students
Naveen Kumar
PhD Student
M.Sc. (Department of Genetics, University of Delhi)
Year of Joining: Aug 2014
Title of Project: Role of Acetyltransferases in GBM
Email: nk415031@gmail.com
Shreoshi Sengupta
PhD Student
M.Sc. (Biochemistry)
University of Calcutta
Year of Joining: Aug 2015
Title of Project: Investigation of tumour cell secretome: Role of differentially abundant proteins in Glioma
stem-like cells (GSCs) and Differentiated glioma cells (DGCs) secretome in modulating Glioblastoma angiogenesis.
Email: shreoshisengupta@gmail.com
Bidisha Prajapati
PhD Student
M.Sc. (Biochemistry)
University of Calcutta
Year of Joining: Aug 2016
Title of Project: Deciphering the role and regulation ofMETTL3 mediated m6A modification in Cancer
Jayita Goswami
PhD Student
M.Sc. (Genetics and plant Breeding)
Bidhan Chandra KrishiViswavidyalaya
Year of Joining: Aug 2017
Title of Project: * To investigate the potential therapeutic role of calcitonin-CALCR axis against glioblastoma*Regulation of Notch signaling pathway by IMP3 (Insulin-like growth factor 2 mRNA binding protein 3)
Email:jayitag22@gmail.com
Arani Mukherjee
PhD Student
Bachelor's: B.Sc (Hons) Zoology, University of Delhi
Master's: M.Sc Zoology, University of Delhi
Year of Joining: Aug 2018Title of Project: Genetics and Epigenetics of GliomaEmail:mukh.arani@gmail.com
Pankaj Sonkar
PhD Student
M.Sc. (Botany)
Banaras Hindu UniversityYear of
Joining: Aug 2018
Title of Project: Genetics and Epigenetics of Glioma
Email:pankajsonkar93@gmail.com
Dr. Samarjit Jana
Post Doctoral Fellow
PhD, West Bengal State University.
Year of Joining: 18.06 2018
Project Title: Identification of a novel long non coding RNA Signature in Glioblastoma
Stem-like cells and its role to regulate the metastatic progression
Email: sjtufan1988@gmail.com
Mainak Mondal
Senior Research Fellow
B. Tech Biotechnology, Sir MVIT, Bengaluru
Year of Joining: 22.10.2018
Area of Research: Next Generation Sequencing Analysis
Bhavana
PhD Student
Year of joining: Aug 2019
M.Sc. (Department of Zoology), Panjab University, Chandigarh
Email: bgupta.bhavana@gmail.com
Rochi Saurabh
Project Assistant
M.Sc. Bioinformatics
Central University of South Bihar, Gaya
Year of Joining: 17.11.2020
Area of Research: Data Analysis, Artificial Intelligence
Email: rochiritz@gmail.com
Lekha K.
Project Assistant
M.Sc. (Biomedical genetics),
University of Madras
Year of Joining: 01.06.2018
Area of Research: Animal handling, PCR/qPCR
Email: lekhasiv2403@gmail.com
Kannaiyan Srinivasan
Scientific Assistant (Staff of MCB, IISc)
B.Sc. Chemistry Madras University
Date of Joining: 30.01.1989
Kantharaju G
Multi Tasking staff
Instrumentation and devices
Alumni
Uchurappa Mala
Ankita Lawarde
Vivek Singh Tomar
Anjali Arora
AbhiramiVisvanathan
Vikas Patil
Jagriti Pal
Baisakhi Mondal
Shruti Bhargava
Zahid Nawaz
Dr.Sannu Thomas
Siddikuzzaman
Mamatha B. N.
R. Ayana
Sudhanshu Shukla
Gulrez Chahal
Swaminathan Kumar
Arkal Arjun Rao
Soumya Rao
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Siva arumugam
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Arpana
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Kalaimathi
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Ravishankar
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Smitha
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Sunil
Suvasini Ramaswamy
Vinod
Narendra Wajapeyee
Yashodha
Akshaya Beerappa
Yashna Paul
Shibla Abdulla
Tapan Baral
Available Positions
Research Opportunities
Post-doctoral positions
Students who have completed their PhD or soon to finish successfully as evidenced from publications are encouraged to apply. Application to DBT RA, UGC-Kothari post-doctoral fellowship, IISc Raman Post-doctoral fellowship would be recommended. Prior experience and interest in computational biology and Bioinformatics background is preferable
Published Work
Anjali Arora, Kumaravel Somasundaram
Glioblastoma vs temozolomide: can the red queen race be won?
Cancer biology & therapy. 2019 March 8;20;8;1083-1090
Vivek Singh Tomar, Tapan Kumar Baral, Krishnaveni Nagavelu, Kumaravel Somasundaram
Biochemical and biophysical research communications; 2019 July 12;515;1;241-247
Anjali Arora, Vikas Patil, Paramita Kundu, Paturu Kondaiah, AS Hegde, A Arivazhagan, Vani Santosh, Debnath Pal, Somasundaram K.
Serum biomarkers identification by iTRAQ and verification by MRM: S100A8/S100A9 levels predict tumor-stroma involvement and prognosis in Glioblastoma
Scientific reports. 2019 Feb 26;9;1;2749
Abhirami Visvanathan, Vikas Patil, Shibla Abdulla, Jörg D Hoheisel, Somasundaram K.
N6-Methyladenosine Landscape of Glioma Stem-Like Cells: METTL3 Is Essential for the Expression of Actively Transcribed Genes and Sustenance of the Oncogenic Signaling
Genes. 2019 Feb 13;10;2;141
Anjali Arora, Somasundaram K
Targeted Proteomics Comes to the Benchside and the Bedside: Is it Ready for Us?
BioEssays. 2019 Feb 8;41;2;1800042
Shabir Zargar, Vivek Tomar, Vidyarani Shyamsundar, Ramshankar Vijayalakshmi,Devarajan Karunagaran, Somasundaram K
A Feedback Loop between MicroRNA 155 (miR-155), Programmed Cell Death 4, and Activation Protein 1 Modulates the Expression of miR-155 and Tumorigenesis in Tongue Cancer
Molecular and cellular biology. 2019 January 7;vol:39;(6);e00410-18
Srividya Kumar, Abhirami Visvanathan, Arimappamagan Arivazhagan, Vani Santhosh, Siva Umapathy, Somasundaram K
Assessment of Radiation Resistance and Therapeutic Targeting of Cancer Stem Cells: A Raman Spectroscopic Study of Glioblastoma
Analytical chemistry. 2018 Sep 14;90;20;12067-12074
Yashna Paul, Sannu Thomas, Vikas Patil, Naveen Kumar, Baisakhi Mondal, Alangar S Hegde, Arimappamagan Arivazhagan, Vani Santosh, Kulandaivelu Mahalingam, Somasundaram K
Genetic landscape of long noncoding RNA (lncRNAs) in glioblastoma: identification of complex lncRNA regulatory networks and clinically relevant lncRNAs in glioblastoma
Oncotarget. 2018 Jul 3;9;51;29548
Jagriti Pal, Vikas Patil, Anupam Kumar, Kavneet Kaur, Chitra Sarkar, Somasundaram K
Loss-of-function mutations in Calcitonin receptor (CALCR) identify highly aggressive glioblastoma with poor outcome
Clinical Cancer Research. 2018 March 15;24;6;1448-1458
A Visvanathan, V Patil, A Arora, AS Hegde, A Arivazhagan, V Santosh, Somasundaram K
Essential role of METTL3-mediated m6A modification in glioma stem-like cells maintenance and radioresistance
Oncogene. 2018 Jan 25;37;4;522
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