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 the elucidation of deregulated signal transduction networks that drive the growth and viability of tumor cells. Functional genomics and systems pharmacology are used to derive detailed information about genome-scale expression of genes in cancer cell lines. This is performed under basal growth conditions and when select candidate genes are perturbed with pharmacological agents or by RNAi. Computational methods such as hierarchical clustering are used to identify differentially expressed genes and expression modules (see Figure 1). Candidate genes and signaling pathways are then functionally characterized using cellular and biochemical methodologies (see Figure 2). The ultimate aim is to identify candidate therapeutic targets for poor prognosis cancer types, such as carcinomas of the lung, pancreas and colon.
Current research in the lab seeks to identify KRAS-regulated signaling networks and to use this information to provide mechanistic insight into KRAS-driven tumor progression. 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 to provide benefit for patients with highly aggressive KRAS-driven cancers.
Current research projects in the lab include:
- Functional and mechanistic elucidation of the KRAS-TAK1 signaling network in KRAS-dependent colon cancers.
- Molecular profiling and characterization of KRAS-regulated microRNAs in lung cancer.
- Identification and validation of novel pro-survival kinases in molecular subtypes of pancreatic cancer.
Postdoctoral and graduate student positions are available. Please contact Dr. Anurag Singh directly (firstname.lastname@example.org).