Masashi Mizokami

Brief Biography

I graduated Nagoya City University Medical School, Nagoya Japan at 1976. After the five year clinical training in Gastroenterology and Heaptology, I have studied a molecular evolution under Prof. Gojobori T, National Institute of Genetics, Japan. After then, I have been applying the many molecular evolutionary techniques to the genomics of hepatitis B virus (HBV) and hepatitis C virus (HCV), nearly 400 million in HBV and 170 million in HCV infected people worldwide, both of which causes different clinical manifestations and also different incidence of hepatocellular carcinoma (HCC) worldwide among HBV or HCV infected patients. The different incidences of clinical manifestation and HCC worldwide are speculated to be in HBV and HCV genome and their infected host genome. Therefore, we have started to collect the samples from all over the world and analyzed hepatitis B and C virus genomes by several molecular evolutionary methods. The analysis has shown that HBV and HCV have been classified into several genotypes and their serial sub-genotypes in the world and the different genotype distribution can explain the different clinical manifestations and different incidence of HCC in each area. These data strongly suggests that hepatitis B and C virus genotypes are important clinically to predict the prognosis of infected patients but the genotypes could not explain completely only themselves. According to success of Human Genome Project in 2003 and I transferred to National Center for Global Health and Medicine, Ichikawa Japan at 2008, we started to investigate the analysis both host genome and hepatitis viruses by molecular evolutionary analysis and newly developed genome analyzing techniques in host genome such as genome-wide association study (GWAS) using SNPs searching, next generation sequencer and others, because the different clinical manifestation in the infected patient among several infectious diseases should be thought to be determined by the mutual reaction between a pathogenic organ and their infected host.

Molecular Evolutionary Analysis of Hepatitis C Virus: Its Application to HCV and Host Genome

Hepatitis C virus (HCV) infection is a global public health problem, because 170 million people have already infected globally. HCV causes acute and chronic infection. Acute HCV infection is usually asymptomatic, and spontaneously clear out around 30% of the infected and the rest of them will develop to chronic hepatitis (CH), liver cirrhosis (LC) and finally hepatocellular carcinoma (HCC) within 30 years of HCV infection. These differences in the clinical settings are linked with a single nucleotide polymorphism of IL28B by genome-wide association study (GWA). HCV is a bloodborne virus and transmits through blood transfusion, contaminated syringe and needles and sexual mainly and perinatal infection is uncommon. HCV has already spread out all over the world and are classified into 7 genotypes and 67 subgenotypes by now and their HCV genotype’s worldwide prevalence is different in each countries. One of the clinical important HCV mysteries is a different incidence of HCC, although there have been no association between a prevalence of HCV and incidence of HCC and no association of HCV genotypic different in each country. To investigate the mystery, we applied the molecular evolutionary techniques to HCV genomes from the international Databank, GenBank/EMBL/DDBL. Because all organisms that are self-replicating are constantly evolving at molecular level and the key of evolution is mutation nucleotides that constitute the genome. According the neutral theory of molecular evolution, nucleotide substitution, especially synonymous substitution, occurs at a constant which are called “molecular clock”. Using this theory we estimated a mutation rate to be 1.3x10-3/site/year using H77 and H90 strains. Using the mutation rate, HCV has been estimated to spread out all over the world around 5-700 years ago from Africa. First pandemics of HCV had occurred around 1945-50 in Japan and Spain where high incidence of HCC countries were in the world and estimated to be associated with the social factors, the intravenous methamphetamine abuse in Japan and Civil war in Spain. We have also speculated to be a start of pandemic worldwide to be at 1950’s, 1960’s and 1970’s in Egypt, USA and Russia, respectively although there is no data in Saudi Arabia where HCV genotype 4 is prevalent. These data strongly indicate that HCC due to HCV will increase worldwide and need to treat and eradicate HCV in the HCV infected patients by new potent anti-HCV drugs. Further studies are now on going including whole-genome sequencing of the HCV uninfected and infected and also asymptomatic and HCC patents with HCV.