Life Sciences & Biotechnology
Title : | Deciphering PRC2 linked epigenetic vagaries in Oncohistones mediated T-cell Acute Lymphoblastic Leukemia |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Mayukh Biswas, Presidency University, Kolkata, West Bengal |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | mayukhbiswas.89@gmail.com |
Equipments : | Refrigerated Centrifuge with Rotor
Electronic Balance with accessories |
Details
Executive Summary : | T-cell Acute Lymphoblastic Leukemia (T-ALL) is a aggressive hematological malignancy originating from HeLa cells, causing the transformation of immature T-cell precursors leading to hematopoietic failure. Recent sequencing studies have identified several 'oncohistones', such as H3K27M in DIPG and AML, H3K36M in sarcomas, and H3F3A p.K27R and HIsT1H3G p.K36R in T-ALL. Aberrant epigenetic regulation is a hallmark of cancer, and some mutations often exhibit oncogenic potential by hijacking the epigenetic circuitries governing normal cellular proliferation and differentiation. However, the specific role of these complexes in oncohistones mediated T-ALL pathogenesis is rudimentarily understood. This study aims to understand how the H3K27R mutation modifies the epigenetic backdrop of HsCs by commandeering the PRC2 complex, eventually leading to oncogenic transformation. The study will investigate the cellular and molecular mechanisms of PRC2 regulation in H3K27R leukemias by interrogating the gene expression programs involved in HsC homeostasis. The study will use transcriptomic, proteomic, genomic, and epigenomic analyses in in-vitro and in-vivo models of oncohistones mediated leukemia. Genome-wide and targeted CRIsPR-screens will be used to identify selective vulnerabilities associated with oncogenic H3K27R mutations in T-ALL. Therapeutically targeting de-novo dependencies will lead to curtailment of oncogenic clones leading to disease remission. |
Total Budget (INR): | 50,05,396 |
Organizations involved