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.