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Molecular Genetics

  • Fumio Kishi, MD, PhD Professor and Chairman

Educational Features

The genomic information of living organisms controls various responses by means of regulating gene transcription and subsequent translation. It also controls the different responses to stimuli from outside of the cells. Genetic diversity between individuals may cause resistance and sensitivity to various kinds of diseases that affect human beings. It is important for medical students to understand the etiology and pathological background of disease at the level of human genomic information and to apply this knowledge to practical and clinical medicine. One of our main objectives is to teach students the mechanisms involved in the transmission of genomic information, and that aberration of these mechanisms can result in risk factors and the onset of various diseases and syndromes. In the course of learning about the molecular biology of the gene and cell, we hope to instill in students a sound knowledge of the molecular basis of human diseases in terms of molecular biology and biochemistry.

Main Areas and Themes of Research

Investigation of molecular mechanism for iron metabolism

Iron is an essential molecule for all life, and iron metabolism is tightly regulated with various molecules since iron itself is extremely harmful to all living organisms when present in excess. Our research focuses on the investigation of various transporters that function in iron metabolism. One of these is the divalent metal transporter (DMT1), which we first cloned as a homolog of NRAMP1 (Natural Resistance-associated Macrophage Protein 1) in 1997, and which later was revealed to possess iron transport activity. This molecule has four isoforms, expressed in a tissue and cell-type specific manner, and is indispensable for iron absorption into the body at the duodenum, iron incorporation into the cytosol at peripheral tissues (especially in erythroid cells), and iron recycling in macrophages. Another transporter we are investigating is the heme transporter. Heme is believed to be incorporated into the body by means of a specific transporter(s). To date, two candidate molecules have been identified, HCP1 and HRG-1, and we are initially investigating the precise localization of these molecules. Through this research, we are trying to delineate the regulation system of iron metabolism.

In addition to our study of these transporters, we have focused on hepcidin, a key regulator of systemic iron homeostasis, and are at present working towards the development of a more convenient assay to measure its physiological activity.

Identification of effector molecules of Chlamydophila pneumoniae

In 2000, our research group successfully sequenced the genome of C. pneumoniae J138 by employing the whole genome shot gun technique. Infection by this microorganism is one of the major causes of community-acquired pneumonia and is thought to pose a serious threat to our general welfare. Knowledge of the C. pneumoniae genome sequence could potentially facilitate the development of an effective drug against this organism. With completion of the C. pneumoniae genome project, we are attempting to identify effector molecules of C. pneumoniae using a novel functional high-throughput screening system for pathogen effectors in the yeast Saccharomyces cerevisiae, and demonstrate the causative effects of target molecules in the host cell by C. pneumoniae.