Laboratory of Cancer Pharmacogenomics
Welcome to the Laboratory of Cancer Pharmacogenomics under the direction of Principal Investigator Dr. Anurag Singh.
Research in the Laboratory of Cancer Pharmacogenomics focuses on context dependent mitogenic signal transduction networks that drive proliferation and survival of tumor cells. The lab uses orthogonal and integrated approaches, including functional genomics and systems pharmacology to understand global gene regulatory networks that contribute to cancer pathophysiology. Computational methods including linear modeling and hierarchical clustering are used to identify differentially expressed genes and expression modules in major molecular subtypes of lung, pancreatic and colon cancers (see Figure 1). Candidate genes and signaling pathways are then functionally characterized using cellular, biochemical and pharmacological methodologies (see Figure 2). The ultimate aim is to identify candidate therapeutic targets for poor prognosis cancer types.
Current research in the lab is focused on elucidating oncogenic KRAS-dependent transcriptional networks that coordinately regulate inflammation, autophagy and cell survival. We are also interested in contextual variability in these networks based on tissue lineage and genetic background. Through this approach, we have identified a number of attractive candidate therapeutic targets that can be antagonized to promote cancer cell death in a context-dependent manner, such as the kinase TAK1 in colon cancers. Since effective pharmacological targeting of the mutant KRAS protein has proven challenging, a key translational goal is to identify clinically efficacious small molecule inhibitors against critical nodes in oncogenic KRAS signaling networks.
Current research projects in the lab include:
1. Functional and mechanistic elucidation of the KRAS-MEK-TAK1 proinflammatory signaling network in KRAS-dependent colon cancers.
2. Molecular profiling and characterization of KRAS-regulated microRNAs in lung cancer.
3. Identification and validation of novel pro-survival kinases in molecular subtypes of pancreatic cancer.
4. Subtype classifications and therapeutic target identification in NRAS-mutant melanoma.