​Cancer is a major health burden and a leading cause of death worldwide. Carcinogenesis is a process whereby cells acquire traits that enable them to evade the constraints of normal proliferation control. Despite great efforts and advancements have been made in the past decades in delineating the underlying molecular mechanisms, knowledge on the process of carcinogenesis is far from complete. Cancer is believed to be initiated by genetic lesions, such as point mutation and chromosome gain/deletion, which could lead to aberrant activation of proto-oncogenes and inactivation of tumor suppressor genes. The recent advancement of high-throughput sequencing technologies enable the researchers to decipher the genetic alterations in cancer genome and to identify novel driver mutations. Recently, growing evidences have suggested that epigenetic deregulation is playing an equally important role in human carcinogenesis. Epigenetics, as implied by the Greek prefix, epi- (means “in additional to”), refers to an additional regulatory layer on top of the genetic information stored as DNA sequences. In human genome, 146bp DNA wrapped around core histone proteins to form nucleosome, the basic unit of chromatin which will further condense to form chromosomes during metaphase of cell cycle. Epigenetic regulation is principally mediated through various heritable modifications at nucleotide, histone, and chromatin levels, but without altering the DNA sequence per se. DNA methylation, histone modifications, and chromatin remodeling are three major mechanisms of epigenetic regulation in mammalian cells. The three epigenetic regulatory mechanisms work intimately to determine local higher-order chromatin structure, and thereby switching “on” and “off” gene expression across the genome. Epigenetic regulation is analogous to the “software package” of a computer that controls whether, when, and how the DNA “hardware” operates. Tightly controlled epigenetic regulation is essential for the establishment of lineage specific gene expression pattern during embryonic development and somatic cell differentiation, which enable multicellular organisms to generate different functional cell types with the same genome. Deregulated epigenetic machinery may lead to malignant transformation and cancer development.

 

Our current researches are centered on deciphering the genetic and epigenetic deregulations in liver cancer (Hepatocellular Carcinoma, HCC), which is one of the most common lethal cancers worldwide and is particularly prevalent in Hong Kong and mainland China.