Deva Magendhra Rao A. K.

Academics & Training

PhD – Genetics, University of Madras

Pre-doctoral training – University of Naples, Federico II, Italy

Postdoctoral Fellow – Dept. of Molecular Oncology, Cancer Institute (WIA)

Research Interest

> Role of Non-coding RNAs in Cancer

> DNA Methylaion and Cancer Transcriptomics

> RNA modifications and their application in Cancer Therapy

Overview

Core area of research : Genomics and Epigenetics of Cancer

Dr. Deva Magendhra Rao A. K. holds a PhD in Genetics and works broadly on Molecular Biology of Cancer. The genomic, transcriptomic, and epigenetic basis of cancer are his major interests. He primarily works on the Non-coding RNA (Long non-coding RNAs, MicroRNAs and circular RNAs) expression control and their application in cancer therapeutics. He studies epigenetic modifications of the cancer genome and transcriptome that affect gene transcription and translation process. His laboratory has integrated facilities like Next Generation Sequencing platforms (PacBio and Ion Torrent), workstations, Real-time PCRs and tissue culture unit. He focuses on identifying cancer biomarkers in early-stage tumors and in liquid biopsies for prognostication. His team also works on therapeutic applications of non-coding RNA and methyl modifications in cancer.

• Role of Non-coding RNAs in Cancer:

Breast cancer is the most common malignancy among women, with the highest incidence rate worldwide. Early detection and intervention is the key to reduce the burden of breast cancer. Gene expression changes in the early stages of breast cancer development are unique. We used RNA sequencing to understand the dysregulated non-coding RNAs in breast cancer. Non-coding RNAs comprise of small ncRNAs – microRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) with potential gene regulatory function. Our study was the first to report on lncRNAs that are distinctly expressed in stage 1-2 of breast cancer and we found a strong association with disease prognosis. The circular RNA can be a result of RNA splicing errors that is common in a cancer cell and therefore represent a differentially expressed group of non-coding RNAs. We are classifying circRNAs that could be definitive markers to detect breast cancer early. Our goal is to understand the functional role of the non-coding RNAs and their strategic application in cancer therapeutics.

• Genomic and Transcriptomic Characterization of Right and Left-sided colon cancer:

Colon cancer is the third most common cancer and fourth most leading cause of cancer-related deaths in the world. The consistent rise in the incidence of colon cancer is reported across India. Colon cancers that develop in proximal colon (right side) and distal colon (left side) have different molecular characteristics and histology. The whole transcriptomic characterization gives an understanding of the molecular differences associated with different anatomical origins. The difference in gene expression between the normal and tumor samples identified by Next generation sequencing will lead to the development of therapeutic candidates and biomarkers for diagnosis of colon cancer at an early stage. We have found a distinct set of genes that are differentially expressed between Right and left sided colon cancer.

• Epigenomic and Epitranscriptomic modifications in cancer:

An imbalance in DNA methylation is a hallmark epigenetic alteration in cancer. The conversion of 5-methylcytosine (5-mC) to 5-hydroxymethyl cytosine (5-hmC), which causes the imbalance, results in aberrant gene expression. Genome-wide analysis revealed a unique 5-mC and 5-hmC signature in breast cancer. The differentially methylated regions (DMRs) were primarily concentrated in the proximal regulatory regions such as the promoters and UTRs, while the differentially hydroxymethylated regions (DhMRs) were densely packed in the distal regulatory regions, such as the intergenic regions (>5 kb from TSSs). The novel 5-hmC candidates identified in the study can be promising diagnostic and therapeutic markers for breast cancer. A similar methylation change that occurs in the RNA molecule is the N6-methyladenosine (m6A), a methyl group added to the sixth position of adenosine. This modification plays a crucial structural and functional role in RNA splicing, stabilization, translation, and localization in mammalian cells and has strong relevance to cancer development. Using MeRIP-sequencing we found methyl-modified RNAs specific to colon cancer. The genes that carried methyl modifications were potentially involved in mRNA splicing and translation control of colon cancer.

Ongoing Projects

Genomic and whole transcriptomic characterization of left and right-sided colon cancer

Funded by: DST-SERB (Core Research Grant) Year: 2022-2025

Colon cancer is anatomically divided into left-sided and right-sided types. Molecular characterization of different sided colon cancer using Next-generation sequencing can identify unique genomic variants and gene expression patterns. A more personalized therapy for left-sided and right-sided colon cancer will have an improved treatment response.

Evaluation of circular RNAs dysregulated in early-stage breast cancer and identifying their potential function in breast tumorigenesis

Funded by: Terry Fox Foundation Year: 2024-2027

Circular RNA are distinct group of Non-coding RNAs with less known function in cancer. Identifying novel circular RNAs associated with breast cancer and understanding their function in cancer progression will result in redesigning effective RNA based therapy.

• Mehra N, Sundaram S, Shah P, Rao AK. Epigenetic Role of Long Non-coding RNAs in Multiple Myeloma. Current Oncology Reports. 2025 Jan 3:1-8. https://doi.org/10.1007/s11912-024-01623-5

• Rao AK, Ramasamy D, Thangarajan R, Mani S. The lncRNA MIAT is regulated by NFYA to promote glioblastoma multiforme through the miR-221-3p/SIRT1 axis. Gene Reports. 2024 Mar 1;34:101883. https://doi.org/10.1016/j.genrep.2024.101883

• Ramasamy D, Thippannah M, Maharajan HR, Balaiah M, Seshadri RA, Kodous AS, Herceg Z, Mehta A, Rao AK, Mani S. Transcriptome-wide profiling identifies colon cancer-associated m6A transcripts and potential RNA methyl modifiers. Molecular Biology Reports. 2024 Dec;51(1):299. https://doi.org/10.1007/s11033-024-09217-x

• Kodous AS, Abdel-Maksoud MA, El-Tayeb MA, Al-Sherif DA, Mohamed SS, Ghobashy MM, Emad AM, Abd El‐Halim SM, Hagras SA, Mani S, Rao AK. Hesperidin-loaded PVA/alginate hydrogel: targeting NFκB/iNOS/COX-2/TNF-α inflammatory signaling pathway. Frontiers in Immunology. 2024 Apr 15;15:1347420. https://doi.org/10.3389/fimmu.2024.1347420

• Patel K, Rao DM, Sundersingh S, Velusami S, Rajkumar T, Nair B, Pandey A, Chatterjee A, Mani S, Gowda H. MicroRNA Expression Profile in Early-Stage Breast Cancers. MicroRNA (Shariqah, United Arab Emirates). DOI 10.2174/0122115366256479231003064842

• AboZaid OA, Abdel-Maksoud MA, Saleh IA, El-Tayeb MA, El-Sonbaty SM, Shoker FE, Salem MA, Emad AM, Mani S, Rao AK, Mamdouh MA. Targeting the NF-κB p65/Bcl-2 signaling pathway in hepatic cellular carcinoma using radiation assisted synthesis of zinc nanoparticles coated with naturally isolated gallic acid. Biomedicine & Pharmacotherapy. 2024 Mar 1;172:116274. https://doi.org/10.1016/j.biopha.2024.116274

• Ramasamy D, Rao AK, Rajkumar T, Mani S. Experimental and Computational Approaches for Non-CpG Methylation Analysis. Epigenomes. 2022 Aug 16;6(3):24. https://doi.org/10.3390/epigenomes6030024

• Ramasamy D, Rao AK, Balaiah M, Vittal Rangan A, Sundersingh S, Veluswami S, Thangarajan R, Mani S. Locus-specific enrichment analysis of 5-hydroxymethylcytosine reveals novel genes associated with breast carcinogenesis. Cells. 2022 Sep 20;11(19):2939. https://doi.org/10.3390/cells11192939

• Aarthy R, Rao AK, Patel K, Sridevi V, Rajkumar T, Gowda H, Mani S. Alteration of miR-362-5p and miR-454-3p expression elicits diverse responses in breast cancer cell lines. Molecular biology reports. 2022 Jan;49(1):821-6. https://doi.org/10.1007/s11033-021-06873-1

• Ramasamy D, Deva Magendhra Rao AK, Rajkumar T, Mani S. Non-CpG methylation—a key epigenetic modification in cancer. Briefings in functional genomics. 2021 Sep;20(5):304-11. https://doi.org/10.1093/bfgp/elab035

• Raghu A, Magendhra Rao AK, Rajkumar T, Mani S. Prognostic Implications of microRNA-155,-133a,-21 and-205 in Breast Cancer Patients’ Plasma. MicroRNA. 2021 Sep 1;10(3):206-18. DOI: 10.2174/2211536610666210707114843

• Rao AK, Arvinden VR, Ramasamy D, Patel K, Meenakumari B, Ramanathan P, Sundersingh S, Sridevi V, Rajkumar T, Herceg Z, Gowda H. Identification of novel dysregulated circular RNAs in early‐stage breast cancer. Journal of cellular and molecular medicine. 2021 Apr;25(8):3912-21. https://doi.org/10.1111/jcmm.16324

• Deva Magendhra Rao AK, Patel K, Korivi Jyothiraj S, Meenakumari B, Sundersingh S, Sridevi V, Rajkumar T, Pandey A, Chatterjee A, Gowda H, Mani S. Identification of lncRNAs associated with early‐stage breast cancer and their prognostic implications. Molecular oncology. 2019 Jun;13(6):1342-55. https://doi.org/10.1002/1878-0261.12489

• Arunkumar G, Rao DM, Kuha A, Manikandan M, Prasanna Srinivasa Rao H, Subbiah S, et al. Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma. Oncology Letters. 2018;15(1):649-57. https://doi.org/10.3892/ol.2017.7296

• Rao AKDM, Rajkumar T, Mani S. Perspectives of long non-coding RNAs in cancer. Molecular biology reports. 2017;44(2):203-18. https://doi.org/10.1007/s11033-017-4103-6

• Rao AKDM, Manikandan M, Arunkumar G, Revathidevi S, Vinothkumar V, Arun K, et al. Prevalence of p53 codon 72, p73 G4C14-A4T14 and MDM2 T309G polymorphisms and its association with the risk of oral cancer in South Indians. Gene Reports. 2017;7:106-12. https://doi.org/10.1016/j.genrep.2017.03.003

• Arvinden VR, Deva Magendhra Rao AK, Rajkumar T, Mani S. Regulation and Functional Significance of 5-Hydroxymethylcytosine in Cancer. Epigenomes. 2017;1(3):19. https://doi.org/10.3390/epigenomes1030019

• Arunkumar G, Deva Magendhra Rao A, Manikandan M, Arun K, Vinothkumar V, Revathidevi S, et al. Expression profiling of long non-coding RNA identifies linc-RoR as a prognostic biomarker in oral cancer. Tumour Biology. 2017;39(4). https://doi.org/10.1177/1010428317698366

• Vinothkumar V, Arunkumar G, Revathidevi S, Arun K, Manikandan M, Rao AKDM, et al. TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas. Tumor Biology. 2016;37(6):7907-13. https://doi.org/10.1007/s13277-015-4694-2

• Revathidevi S, Manikandan M, Rao AKDM, Vinothkumar V, Arunkumar G, Rajkumar KS, et al. Analysis of APOBEC3A/3B germline deletion polymorphism in breast, cervical and oral cancers from South India and its impact on miRNA regulation. Tumor Biology. 2016;37(9):11983-90. https://doi.org/10.1007/s13277-016-5064-4

• Manikandan M, Rao AKDM, Arunkumar G, Manickavasagam M, Rajkumar KS, Rajaraman R, et al. Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism. Molecular cancer. 2016;15(1):28. https://doi.org/10.1186/s12943-016-0512-8

• Manikandan M, Rao DM Arunagiri K, Rajkumar KS, Rajaraman R, Munirajan AK. Altered levels of miR‐21, miR‐125b‐2*, miR‐138, miR‐155, miR‐184, and miR‐205 in oral squamous cell carcinoma and association with clinicopathological characteristics. Journal of Oral Pathology & Medicine. 2015;44(10):792-800. https://doi.org/10.1111/jop.12300

• Manikandan M, AK DMR*, Arunkumar G, Rajkumar KS, Rajaraman R, Munirajan AK. Down regulation of miR-34a and miR-143 may indirectly inhibit p53 in oral squamous cell carcinoma: a pilot study. Asian Pac J Cancer Prev. 2015;16(17):7619-25. https://doi.org/10.7314/APJCP.2015.16.17.7619

• Rao AK, Vinothkumar V, Revathidevi S, Arunkumar G, Manikandan M, Arun K, et al. Absence of the TP53 poly-A signal sequence variant rs78378222 in oral, cervical and breast cancers in South India. Asian Pacific journal of cancer prevention: APJCP. 2014;15(21):9555. https://doi.org/10.7314/APJCP.2014.15.21.9555

• Manikandan M, AK DMR, Munirajan AK. Analyzing the expression of candidate microRNAs in primary tumors of oral squamous cell carcinoma. Molecular cytogenetics. 2014;7(S1):P7. https://doi.org/10.1186/1755-8166-7-S1-P7

• Rajkumar K.S. AKG, Deva Magendhra Rao, Rajaraman R., Munirajan A.K. Uroporphyrinogen decarboxylase gene expression in oral squamous cell carcinomas. J Clin Oncol. 2013(suppl; abstr e17002). DOI: 10.1200/jco.2013.31.15_suppl.e17002

• Maria D. Castellone AV, Deva Magendra Rao, Marialuisa Sponziello, Dora Fabbro, Magesh Muthu, Cosimo Durante, Marianna Maranghi, Giuseppe Damante, Stefano Pizzolitto, Giuseppe Costante, Diego Russo, Massimo Santoro, Filetti S. A novel de novo germ-line V292M mutation in the extracellular region of RET in a patient with phaeochromocytoma and medullary thyroid carcinoma: functional characterization. Clinical Endocrinology. 2010;73:529-34. https://doi.org/10.1111/j.1365-2265.2009.03757.x

• Castellone MD, De Falco, V., Rao, D.M., Bellelli, R., Muthu, M., Basolo, F., Fusco, A., Gutkind, J.S., Santoro, M. The beta-catenin axis integrates multiple signals downstream from RET/papillary thyroid carcinoma leading to cell proliferation. Cancer Res. 2009;69:1867-76 https://doi.org/10.1158/0008-5472.CAN-08-1982

Ms. Hema Raja Pushpam

Dr. N.V. Vani

Ms. Ezhila Subramanian

M.Sc or PhD in Molecular Biology/Genetics/Bioinformatics or life sciences completed candidates with fellowships from CSIR/DBT/DST/ICMR or other funding agencies can approach for positions.

To apply visit /career

Contact: PI/Lab email

ak.devamagendhrarao@cancerinstitutewia.org