Genomic and Targeted Approaches for Cancer Gene and Therapeutic Target Discovery
Cancer is complex disease, which involve alternation of multiple genetic and epigenetic factors and pathways in normal cells for them to become cancerous. Because of its complex nature and the ability of cancer cells to evolve rapidly undertreatment, cancer treatment with durable outcome is a challenging problem. Therefore, in-depth molecular understanding of cancer initiation and progression is necessary for developing effective therapies. In-order to identify and characterize critical cancer vulnerability genes and their downstream network we use genomic and targeted approaches. Our key areas of research are-
Identification of novel Tumor Suppressors and Oncogenes using Large-scale Functional Genomics Screens
Tumor suppressor genes and oncogenes are two key classes of genes that are shown to have important roles in cancer growth and progression. Most cancers show activation of multiple oncogenes and inactivation of tumor suppressor genes. Our goal is to identify tumor suppressor genes and oncogenes using functional genomics approaches of shRNA, CRISPR/CAS9-based and/or ORFome-based library screening. We also screen patient sample dataset to identify the important genes that are necessary for cancer growth and progression. These screens utilizes both in vitro and in vivo approaches using both human and mouse model-based systems.
Understanding the mechanism of action of novel Tumor Suppressors and Oncogenes
The second important objective is to determine how certain oncogenes and tumor suppressor genes function to drive cancer initiation and progression. To do so, we employ assay that could measure global changes both qualitatively and quantitively in DNA, RNA and protein content of the cells. These assays include next generation sequencing based assay like ATAC seq, RNA seq, mass spectrometry among others. These studies provide an insight into the mechanism/signaling by which these Oncogenes/tumor suppressors cause predisposition to a variety of cancer.
Targeting Cancer Vulnerability Genes and Pathway for Improving Cancer Treatment
Due to complex nature of cancer, achieving durable and effective response to the treatment in most cancers has been a difficult goal. Therefore, there is urgent need to develop new and effective therapeutic approaches for successful cancer treatment. Thus, identifying new drug targets and improving the existing therapeutic approaches to make them more effective is important for developing next generation of cancer therapies. Therefore our ultimate goal is to identify targetable cancer vulnerability genes and test their potential clinical utility using pre-clinical mouse models of cancer with the goal of providing effective cancer therapy. Targeting of these new cancer vulnerability genes either alone or in combination with existing therapy will most likely successfully impact treatment of a large percentage of human cancers.