There has been a paradigm shift in biology in the past decade. One of the most exciting changes is the emerging concept of ‘Epigenetics’ beyond 'Genetics'. Epigenetics seeks to understand complex biological phenomena at a different angle and aims to exceed the limits of genetics. The main focus of genetics research has been identifying DNA mutations and the factors that cause such genetic mutations. On the other hand, epigenetics research focuses on understanding gene expressions at the level of chromatin which is composed of DNA and histones. In the field of epigenetics, it is important to understand how histone modifications regulate gene expressions.
Our body tries to maintain a steady state of balance, called ‘homeostasis’, and it is important to question how epigenetic mechanisms function in terms of maintaining homeostasis. Understanding epigenetics which is essential for maintaining homeostasis would be crucial for tracing back which perturbation signals have interrupted the homeostasis and caused the disease. Such diseases can be classified as ‘epigenetic diseases’. Cancer is the most well-studied epigenetic disease, but recent studies have revealed that other diseases including immune disorders induced by inflammation and neurodegenerative diseases which are associated to autophagy, could also be classified as epigenetic diseases. Autophagy is an essential self-digestion process to maintain homeostasis and promote survival in response to starvation, and activation of specific epigenetic programs is indispensable for a sustained autophagic response.
We aim to understand the role of epigenetic regulatory mechanisms in health and epigenetic disease. For this, we will discover novel epigenetic code and regulators, determine their functions in homeostasis, explore mechanisms of their disturbance in diseases, and generate a functional 3D (Epigenome-Trascriptome-Proteome) map of epigenetic diseases for rational design of therapeutic strategies. In sum, we will study epigenetic diseases, investigate causality of the relationship between the epigenetic code and diseases, perform epigenetic drug screenings for therapeutic applications, and validate the efficacy and toxicity of the drug. We will initiate new challenging projects to identify novel epigenetic code and regulators and determine their in vivo functions using mouse models. The results will be integrated at the epigenomic, transcriptomic, and proteomic level. Big data and deep-learning will be applied for multidisciplinary research.
Specific Aims
Specific Aim 1: To understand the roles of the epigenetic code in homeostasis and molecular mechanisms of its perturbations leading to epigenetic diseases
Specific Aim 2: To understand the roles of the epigenetic code in regulation and molecular mechanisms of cancers, autophagy and inflammation
Specific Aim 3: To identify novel epigenetic regulators and determine their physiological and pathological functions using mouse models
Specific Aim 4: To chart a functional 3D map of epigenetic diseases and develop ‘Epigenetic diseases-on-a-chip’ to perform screening of epigenetic drugs for range of therapeutic application