Epigenetic biology can be defined as a collection of inherited cellular cues whose alterations can establish different patterns of gene expression and thus differentiate fates of individual cells in the context of the identical genome. Among important epigenetic players are >60 human protein methyltransferases (PMTs), > 30 protein lysine demethylases (KDMs), and various methyl-arginine/lysine (Rme/Kme) reader proteins. These epigenetic modulators collectively maintain normal cellular functions and their dysregulation is frequently associated with diseases. To perturb epigenetic axes, efforts have been made on developing inhibitors against specific PMTs, KDMs and Rme/Kme readers.
Given broad biological impact of Rme/Kme-involved epigenetics, much attention has been given to reveal molecular mechanisms, cellular outcomes and biological contexts of diverse epigenetic events. However, conventional approaches are often insufficient to portrait complexity of Rme/Kme-regulated epigenetics. The resulting knowledge gaps hinder systematic understanding of epigenetic roles under normal and disease settings. Developing need-driven technologies and implementing them to bridge the knowledge gaps can be essential for advancing discovery research of epigenetic biology.
The Luo Lab is interested in discovery research at the interface of chemistry and biology. From chemical perspective, we have established a research track in identifying important biological questions that cannot be readily probed with conventional methods alone but can be interrogated with innovative chemical tools. In regard with our interest in discovery biology, the overall goal of my laboratory is to implement integrated tools to annotate Rme/Kme-involved epigenetics with emphasis on novel molecular mechanisms and biological outcomes. Given the technology and knowledge gaps described above, it is yet ready to systematically interrogate Rme/Kme-involved epigenetics with fully-resolved PMT-methylome-effector networks. We therefore envision dissecting the complex networks into chemical biology-feasible research modules (e.g. PMT-methylome; methylome-effector networks) for functional annotation. In the context of metastatic cancer, cell differentiation and neural diseases, we focus on epigenetic writers (PMTs), readers (Rme/Kme effectors) and erasers (demethylases) with functional relevance to noncanonical histone methylation, protein homeostasis and transcription plasticity.
In parallel, the Luo lab is interested in developing potent, target-specific small-molecule epigenetic modulators as structural or chemical probes, pharmacological candidates and anti-cancer reagents. For these projects, we collaborate with structural biologists, computational biologists, caner biologists and physicians to formulate innovative concepts and approaches to identify and address emerging epigenetic questions. Our ambitious vision is to build up a highly integrated platform at the interface of chemistry and biology and advocate it to reveal epigenetic biology and target druggable epigenetic processes for cancer therapy.