Hideo Watanabe, M.D., Ph.D.
Icahn School of Medicine at Mount Sinai
Funded by the American Lung Association of the Northeast
Understanding the Complexity and Variability of Lung Tumors
To improve precision and efficacy of current target-based lung cancer treatment, it is critical to further distinguish different subgroups of lung cancer. We will study factors that are essential during the formation of the lung and control the identity of lung cells in adults. We will identify novel subsets of lung cancers that rely on those factors by focusing on a specific molecular feature, histone marks on DNA. In addition, to understand the complexity, variability and adaptability of the tumor, we aim to develop a system to profile such features on thousands of individual cells. The results could provide a foundation for a new paradigm in lung cancer diagnostics and therapeutics.
Update: DNA sequences called enhancers have the ability to greatly increase the expression of genes in their vicinity. We have been able to build a novel way to divide lung cancers into groups based on our enhancer profiles, which has provided rich information regarding cellular lineage-specific enhancer regions. From those data, we have been able to nominate candidate super-enhancers most differentially enriched and signifying a subclass that may have potential therapeutic implications. We are also getting closer to developing a new genome technology that could address intriguing questions of cell identity variability of the cancer cells.