Mohammad Fallahi-Sichani's research area is in systems pharmacology and the complex responses of cancer cells to therapeutic interventions, particularly the drug resistance of cells and tumors to chemotherapy. In May, he received a new National Institutes of Health R01 award to better understand the interplay between genetic, epigenetic and signaling mechanisms that determine the state of MAP kinase (MAPK) pathway dependency in tumor cells.In BRAF-V600 mutated melanomas, hyperactivation of MAPK signaling has motivated the clinical use of MAPK-targeted therapies, but they often lead to variable responses and no durable cure in most patients. NIH R01CA249229The award's Public Health Relevance Statement reads, "The discovery of BRAFV600E oncogene in a wide range of human cancers, including >50% of melanomas, has provided opportunities for the development of BRAF and MAPK-targeted cancer therapies, but their benefit has been limited due to tumor-to-tumor and cell-to-cell heterogeneity in the state of BRAF/MAPK dependency. Heterogeneity is regulated by a mixture of genetic, epigenetic, and signaling mechanisms, whose interplay with one another determines the dynamic state of MAPK dependency in tumor cell populations. This study creates a platform to characterize the role of epigenetic factors associated with tumor differentiation state and tissue lineage, with the goal of developing predictive tools to modulate the epigenetic state of BRAF/MAPK dependency in tumor cells and ultimately improving the clinical benefit of MAPK-targeted therapies in patients with BRAF-mutated cancers."