Barry H. Paw, M.D., Ph.D.
Year elected: 2008
Current membership category: Senior
Associate Professor, MedicineBrigham & Women’s Hospital, Harvard Medical School
Harvard Institutes of Medicine Bldg.
77 Avenue Louis Pasteur, HIM 616
Boston, MA 02115-5727
United States of America
Phone: (617) 525-4971
Genetics of Blood Cell Development The focus of our laboratory research is studying genes important for red cell development, in particular iron and heme metabolism, using the zebrafish as a model organism. The genetic program for development of the hematopoietic system is conserved from zebrafish to higher organisms. Using the advantages of zebrafish genetics and developmental biology, we have undertaken genetic screens to isolate zebrafish mutants with anemia. The genes disrupted in these mutants are identified by positional and candidate cloning strategies to gain insight into the genetic basis of vertebrate hematopoiesis. The biological functions of the identified genes are studied in zebrafish embryos and complementary model systems, such as mouse (cultured cells and transgenic mice) and yeast. Mitochondrial Iron Metabolism Our group has identified the gene disrupted in the frascati mutation as a novel mitochondrial metal transporter, Mitoferrin (Mfrn, Slc25A37), crucial for erythropoiesis. Loss of function of the Mitoferrin transporter results in severe anemia and an erythroid maturation arrest due to defects in mitochondrial iron assimilation. The function of this gene is highly conserved from yeasts to zebrafish and mammals. Our group is investigating the biochemical properties of the Mitoferrin transporter in zebrafish, mouse, yeast, and cell culture models. Our group has identified the association between patients with anemia and hepatic failure with a nonfunctional, mispliced Mitoferrin mRNA. This example proves the utility of genetic screens in zebrafish as a means for gene discovery and uncovering the genetic basis of diseases.
Harvard Medical School, Brigham & Women's Hospital (Primary)
Anna Greka, MD, PhD is the representative at this institution.