RESEARCH 

Assertive discoveries have been carried out during the past decade to explore the role of epigenetic mechanisms for the regulation of cellular phenotype. This regulation provides the software that packages DNA, modifications in gene expression without changing the DNA sequence of a gene. These are called epigenetic alterations. These alterations include methylation, acetylation, phosphorylation and ubiquitylation of DNA and histone proteins (nucleosomes) as well as chromatin remodelling. “Epigenetics” refers to heritable changes in gene expression patterns without changing the primary DNA sequence. Technological advancements in genome-wide DNA sequencing, RNA sequencing for coding and non-coding expression patterns, DNA methylation and chromatin assay and assessment of all of the above with advance bioinformatics tools are facilitating to delineate the cancer epigenome and permit key insights for developing personalized therapeutics. Our lab basically focuses on cancer epigenetics and we are trying to decipher the epigenome regulation that may lead to development of new epigenetic therapeutic drugs.  The recent discovery of Cancer Testis/Germline (CT/CG) antigen expression in cancer suggests a strong link between gametogenesis and carcinogenesis.CG antigens have the potential to serve as biomarkers for cancer stem cells and potential targets in cancer metastatic processes as well as in the recurrence of cancer after chemotherapy. We are indulging to open the new avenues for novel Cancer Testis/Germline (CT/CG) POTE antigens to be used for cancer immunotherapy for treating gynaecological cancer patients for better reproductive health. POTE (Prostate, Placenta, Ovary, and Testis-expressed) is a recently discovered gene family consisting of 13 autosomal and pericentromeric localized cancer-testis/germline antigen genes. The POTE paralogs gene family encodes proteins with cysteine-rich (CRR) domains, ankyrin repeat motifs and α-helical regions. It is established that epigenetic mechanisms control expression of CT/CG antigens. Epigenetic modulatory agents robustly promote expression of CG antigens, as well as the class-1 histocompatibility complex (MHCI).Thus, we emphasize the possible clinical use of epigenetic modulators to augment the immunotherapeutic potential of POTE family antigens, and how this will ultimately improve strategies for cancer detection and treatment.

 

Towards the mechanistic part, we are working on chromatin dynamics to be applied for answering key questions of alteration in pericentromeric localized gene expression during cancer. POTEs gene family are localized at pericentromeric regions, where duplicated genes are often abundant. Still, it is not clear how POTE paralogs escape pericentromeric repression and become expressed in cancer. Chromatin has a defined 3-D organization inside the nucleus, which guides gene expression. Although this 3D Genome organization is just recently being defined to the molecular levels, there is much to be answered in this area. Our lab is working to correlate the established molecular mechanisms for gene regulation e.g DNA methylation to be linked to the 3D genome organization inside the nucleus. It is known that there are several repressive compartments inside the nucleus where genes are dynamically located as a whole. Therefore what is the relation of epigenetic gene regulation to the gene localization and arrangement inside the nucleus? This is an inevitable question here. One such repressive compartment is nuclear lamina, where the associated sequences, called "Lamina-associated domains (LADs)" and “pericentromeric-associated domains (PADs)”are dynamically placed. We are trying to find factors, responsible for these LADs /PADs formation and regulation to be applied for cancer biology. Altogether this is an entirely new area in the field of cancer biology and studies are coming with new fascinating facts, and we are trying to be part of these strategies, with an ultimate goal to combat cancer.

Funded Projects:
  1. Artificial Intelligence in Oncology: Harnessing big data and advanced computing to provide personalized diagnosis and treatment for Cancer patients.                                             Funded by: Ministry of Information Technology (2019-2021).

  2. Interplay between Cancer Testis/ Germline POTE antigen and NOTCH Signaling and its association with Global DNA Methylation in Ovarian Cancer.                                     Funded by:ICMR- MOHFW (2019-2022)

  3. Genome-Wide DNA Methylation & Genomic Instability Profiling and Evaluating Its Potential as a Biomarker and Immunotherapeutic Target for Ovarian tumor

     Funded by: Department of Biotechnology, Ministry of Science and Technology, New                  Delhi, India, Duration: 5 years,

4.  Nuclear Architecture as an Epigenetic Regulator in Pericentromeric localized Cancer-              Testis/Germline Antigen POTE Expression in Ovarian Cancer

     Funded by: Department of Science &Technology, Ministry of Science and Technology (New      Delhi, India), Duration: 3 years

5.  Estimate the Serum Levels of Cancer-Testis Antigen POTE as a Biomarker in Epithelial              Ovarian Cancer.

     Funded by: AIIMS Intramural Grant, Duration: 2 years.

6.  A pilot study to analyze serum levels and intra-tumour expression of cancer-testis antigen        POTEE as a new biomarker for ovarian cancer

     Funded by: Department of Health Research, Ministry of Health and Family Welfare,                  Government of India, Duration: 2 years.

7.  Molecular Characterization of Endometrial Cancer and its correlation with clinico-                    pathological Features

     Funded by: AIIMS, Intramural Collaborative Research Grant,

Contact Us:

Lab. No 3029,

Department of Biochemistry,

All India Institute of Medical Sciences,

Ansari Nagar, New Delhi-110029,

Delhi, Bharat (India).

Email: ashok.sharma@aiims.edu

Phone: +91-11-26593545

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