Prof. Vijayalakshmi Mahadevan

Research Focus Key Words

Chromatin and Epigenetics, Disease Epigenetics, p53 mutations in cancer, epigenetic inhibitors, cancer epigenetics, imaging, machine learning

Background

With a background in Physics and Electronics from Bharathidasan University, Trichy, Dr.Vijayalakshmi Mahadevan completed her Ph.D. from the National Centre for Biological Sciences – Tata Institute of Fundamental Research( NCBS-TIFR), Bangalore. She was an Assistant Professor in the School of Electrical and Electronics Engineering at SASTRA Deemed University in Thanjavur and subsequently a TCS Chair Professor of Bioinformatics and Associate Dean of the School of Chemical & Biotechnology. She was the Group Lead of the Chromatin and Epigenetics group, and also headed the Department of Bioinformatics from 2008 to 2016 besides being affiliated to the Centre for Nanotechnology and Advanced BBiomaterials (CeNTAB) at SASTRA.

In addition, Dr.Vijayalakshmi was a Research Mentor in the National Network for Mathematical and Computational Biology (NNMCB), India from 2013 and was a Research Mentor – Research Science Initiative (RSI) of the IIT-Madras, Chennai Mathematical Institute, SASTRA University, Thanjavur, PSBB Group of Schools, Chennai and Centre for Excellence in Education, McLean, USA to promote scientific research among school children.

Education

1. Ph.D: National Centre for Biological Sciences
2. Postdoctoral Research: Tata Institute of Fundamental Research (NCBS-TIFR), Bangalore (2008)

Professional Experience

Professor and Associate Dean –School of Chemiscal and Biotechnology, SASTRA Deemed University, Thanjavur (till January 2016) 

Research Interest Profile

1. Investigating genome wide enrichment of epigenetic modifications influenced by p53 mutations in colon cancer
   Alterations in epigenetic modifications and chromatin structure are known to drive tumour initiation and progression. Though genetic regulation and mutations in several oncogenes have been extensively reported in colorectal cancer; epigenetic events that drive oncogenic functions are not clearly understood. Colorectal cancer shows 40-50% mutations in tumour suppressor p53 that lead to early onset of tumour, aggression, higher metastatic potential and development of resistance to conventional therapies. The clinical importance of p53 mutations in colon cancer emphasises the need to understand the interplay between p53 signalling and epigenetic regulation in colon cancer. A recent work in the lab has identified the elevation in the levels of the repressive histone modifications in colon cancer cells that lack p53 or those that express p53 mutations. High throughput and high resolution imaging point to alterations in nuclear morphology and significant increase in heterochromatin volume in these cells. In order to identify the genome wide enrichment of the repressive and active chromatin marks, RNAPolI and heterochromatin protein HP1-α and to identify their differential binding in p53 wt and p53null/mutant CRC cells, ChIP sequencing has been initiated. Interesting observations of the localisation of the epigenetic marks from nuclear periphery and heterochromatin spot distribution necessitates probing of the methylation machinery further and hence to study LADs (Lamin Associated Domains) and chromatin organisation using 4C techniques.
2. Understanding alterations in the EMT genes upon bromodomain inhibition
   BET bromodomain inhibitors are a recently developed class of epigenetic drugs that target epigenetic reader domains. These inhibitors have shown significant success in targetting haematological malignancies while little evidence is available on its efficacy in solid tumours. Our recent work on epigenetic alterations induced by BET inhibitor JQ1 in colon cancer cells showed p53 dependent reduction in the levels of H4 acetylation and increase in heterochromatin associated H3K9me3 in colon cancer cells. Since BET inhibitors are known to overcome drug resistance, it is also interesting to understand how these inhibitors alter the profile of genes involved in Epithelial to Mesenchymal Transition (EMT).  RNA sequencing on colon cancer cells treated with bromodomain inhibitors at 48 hours will be done to understand the changes in expression profiles of the EMT genes.
3. Epigenetic alterations in Neuropsychiatric disorders
   
   

Group members

1. Harsha Rani, Ph.D. student
2. Shreya Sharma, Ph.D. student
3. Divya Selvakumar
4. Prakruthi M. Hegde

Collaborators:

1. Dr. Dimple Notani, NCBS-TIFR, Bangalore
2. Prof. Regine Schneider Stock, Head-Tumour Pathology, University of Erlangen, Nuremberg, Germany
3. Prof. Thomas Brabletz, Professor  of Molecular Oncology Department  of Experimental Medicine, University of Erlangen, Germany
4. Dr. Shamik Sen, IIT- Bombay
5. Dr. Mohit Kumar Jolly, Indian Institute of Science, Bangalore
6. Dr. Jagannath Dixit, HCG Bangalore

Publications and Patents:

1. Regine Schneider-Stock; Pablo Lindner; Sushmita Paul; Markus Eckstein; Julienne K Muenzner; Katharina Erlenbach-Wuensch; Ahmed Husayn; Vijayalakshmi Mahadevan; Thomas Brabletz; Arndt Hartmann; Julio Vera ,
   EMT transcription factor ZEB1 alters the epigenetic landscape of colorectal cancer cells (Under Revision)
2. Maiuthed A, Ninsontia C, Erlenbach-Wuensch K, Ndreshkjana B, Muenzner JK, Caliskan A, Husayn AP, Chaotham C, Hartmann A, Vial Roehe A, Mahadevan V, Chanvorachote P,
   Schneider-Stock R.Cytoplasmic p21 Mediates 5-Fluorouracil Resistance by Inhibiting Pro-Apoptotic Chk2, Cancers, 10(10), 373,2018
3. Mahalakshmi Ramadoss, Vijayalakshmi Mahadevan,
   Targeting the cancer epigenome: synergistic therapy with bromodomain inhibitors, Drug Discovery Today, Vol.23,76-89, 2018
4. Judith Mary Hariprakash, Shamsudheen Karuthedath Vellarikkal, Ankit Verma, Anop Singh Ranawat, Rijith Jayarajan, Rowmika Ravi, Anoop Kumar, Vishal Dixit, Ambily Sivadas, Atul Kumar Kashyap, Vigneshwar Senthival, Paras Sehgal, Vijayalaskhmi Mahadevan, Vinod Scaria, Sridhar Sivasubbu ,
   SAGE- a comprehensive resource of genetic variants integrating South Asian genomes and exomes, Database, 2018, 1: 1-10.
5. Mahalakshmi R, Husayn Ahmed P, Vijayalakshmi Mahadevan,
   HDAC inhibitors show differential epigenetic regulation and cell survival strategies on p53 mutant colon cancer cells, Journal of Biomolecular Structure and Dynamics,2018, 36(4):938-955
6. Krithika A Shankaran, Shabir Ahmad Ganai,… Vijayalakshmi Mahadevan,
   In silico and In vitro evaluation of the anti-inflammatory potential of Centratherum punctatum Cass-A, Journal of Biomolecular Structure and Dynamics, 2016, 35(4): 765-780.
7. Rajendra Kristam, Shashidhar N.Rao, Anne Sudha D’Cruz, Vijayalakshmi Mahadevan, Vellarkad N,Viswanadhan,
   TRPV1 antagonisms by piperazinyl –aryl compounds : A Topomer-CoMFA study and its use in virtual screening for identification of novel antagonists, 2017, J Mol Graph Model 72:112-128.
8. Natalya Benderska, Anna-Lena Dittrich, Sabine Knaup, Tilman T. Rau, Clemens Neufert, Sven Wach, Fabian B. Fahlbusch, Manfred Rauh, Ralph M. Wirtz, Abbas Agaimy, Swetha Srinivasan, Vijayalakshmi Mahadevan, Petra Rümmele, Emmanouela Rapti, Maria Gazouli, Arndt Hartmann, Regine Schneider-Stock,
   miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis,  Inflammatory Bowel Diseases, 2015, 21(9): 2039-51 ( IF :4.464)
9. Shabir Ahmad Ganai, Mahalakshmi Ramadoss and  Vijayalakshmi Mahadevan,   
   Histone Deacetylase (HDAC) Inhibitors  –  emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration, Current  Neuropharmacology,  2015,  Volume 13 ( Epub ahead of print) ( IF: 3.049)
10. Shabir Ahmad Ganai, Karthi Shanmugam,Vijayalakshmi M,
    Energy optimized pharmacophore approach to identify potential hotspots during inhibition of Class II HDAC Isoforms,  Journal of Biomolecular Structure and Dynamics, 2015, 33(2): 374-87  ( IF: 2.919)
11. Ganai SA, Kalladi SM,  Vijayalakshmi M, 
    HDAC inhibition through  Valproic acid modulates the methylation profiles in human embryonic kidney cells,  Journal of Biomolecular Structure Dynamics, 2015, 33(6):1185-97 ( IF:2.919)
12. Lowrence Rene Christena, Shankar Subramaniam, Mohan Vidhyalakshmi,  Vijayalakshmi Mahadevan, Aravind Sivasubramanian, Saisubramanian Nagarajan,
    Dual role of pinostrobin-a flavonoid nutraceutical as an efflux pump inhibitor and antibiofilm agent to mitigate food borne pathogens, Royal Society of Chemistry Advances, 2015, 5: 61881-61887 ( IF: 3.84)
13. Garg M, Ramdas N, Vijayalakshmi M, Shivashankar GV, Sarin A,
    The C-terminal domain (CTD) in linker histones antagonizes anti-apoptotic proteins to modulate apoptotic outcomes at the mitochondrion, Cell Death and Disease, 2014, 5: e1058 ( IF : 5.014)
14. Natalya Benderska, Jelena Ivanovska, Tilman T Rau, Jan Schulze-Luehrmann, Suma Mohan, Saritha Chakilam, Muktheshwar Gandesiri, Elisabeth Zische, Thomas Fischer, Abbas Agaimy, Luitpold Distel, Heinrich Sticht,  Vijayalakshmi Mahadevan, and Regine Schneider-Stock,
    DAPK-HSF1 interaction as a new positive feedback loop for TNF-induced apoptosis in colon cancer cells,  Journal of Cell Science, 2014, 127: 5273-5287  (IF: 5.432)
15. Chirine El-Baba,  Vijayalakshmi Mahadevan, Fabian B Fahlbusch, Suma Mohan S, Tilman T Rau, Hala Gali-Muhtasib, Regine Schneider-Stock,
    Thymoquinone-induced conformational changes of PAK1 interrupt prosurvival MEK-ERK signaling in colorectal cancer, Molecular Cancer, 2014, 13(201): 1-14 ( IF: 4.257)
16. Raghu R, Devaraji V, Leena K, Riyaz SD, Rani PB, Kumar BS, Naik PK, Dubey PK, Velmurugan D, Vijayalakshmi M 
    Virtual screening and discovery of novel Aurora Kinase inhibitors, Current Topics in Medicinal Chemistry, 2014, 14(17): 2006-19 ( IF: 3.402)
17. Jelena Ivanovska,  Vijayalakshmi Mahadevan, Regine Schneider-Stock, DAPK and cytoskeleton-associated functions, Apoptosis, 2014, 19(2): 329-38 ( IF:3.685)
18. Saritha Chakilam, Muktheshwar Gandesiri, Tilman T Rau,  Vijayalakshmi Mahadevan, Jelena Ivanovska, Ajithavalli Chellappan, Margret Rave-Fränk, Hans Christiansen, Arndt Hartmann, Pablo Steinberg, Regine Schneider-Stock,
    Death-Associated Protein Kinase Controls STAT3 Activity in Intestinal Epithelial Cells,  American Journal of Pathology, 2013, 182(3): 1005-20 (IF: 5.071)
19. Jelena Ivanovska, Alexandra Tregubova,  Vijayalakshmi Mahadevan, Saritha Chakilam, Muktheshwar Gandesiri, Natalya Benderska, Benjamin Ettle, Arndt Hartmann, Stephan Söder, Elisabeth Ziesché, Thomas Fischer, Lena Lautscham, Ben Fabry, Gabriela Segerer, Antje Gohla, Regine Schneider-Stock,
    Identification of DAPK as a scaffold protein for the LIMK/cofilin complex in TNF-induced apoptosis,  The International Journal of Biochemistry & Cell Biology, 2013, 45: 1720-1729 (IF: 4.05)
20. Annapurna HV, Apoorva B, Arun KP, Brindha P, Swaminathan S,  Vijayalakshmi M, Nagarajan A,
    Isolation and in silico evaluation of antidiabetic molecules of Cynodon dactylon (L.), Journal of Molecular Graphics and Modelling, 2013, 39: 87-97 (IF: 1.722)
21. Vijayalakshmi  M,  G.V.Shivashankar, R.Sowdhamini,
    Simulations of Core Histone Modifications on Human Mono Nucleosomes Reveal Alterations in Stability,  Journal of Biomolecular Structure &Dynamics, June 2009 ( IF:2.919)
22. Vijayalakshmi M,  Shivashankar GV, Sowdhamini R,
    Simulations of SIN mutations and histone variants in human nucleosomes reveal altered protein-DNA and core histone interactions,  Journal of Biomolecular Structure & Dynamics, 2007, 25:207-218 (Cover Page) (IF:2.919)

Book Chapters

1. Harsha Rani and Vijayalakshmi Mahadevan,
   Histone and DNA Methylome in neurodegenerative, neuropsychiatric and neuro developmental disorders ,The DNA, RNA, and Histone Methylomes, Springer Nature (2019) (In Press)
2. Shabir A Ganai, Shashwath Malli K, Vijayalakshmi Mahadevan, Exploring Nuclear Lamin – Chromatin interactions and their signalling cascades, Encyclopedia of Molecular Life Sciences, Springer Inc., Article ID: 367350; Chapter ID: 580. (2014)
3. Vijayalakshmi Mahadevan and Swaminathan Sethuraman, Nanomaterials and Nanosensors for Medical Applications, Trends in Nanoscale Mechanics, ICASE/LaRC Interdisciplinary Series in Science and Engineering, Volume 9, 2003, pp 207-228