Mark D. Fleming

Department of Pathology
Children's Hospital
Enders 1116.1
Boston, MA 02115
Tel: (617) 919-2664
Fax: (617) 730-0168
Email: mark.fleming@childrens.harvard.edu
My laboratory is primarily interested in investigating how erythroid cells normally acquire and utilize iron. In mammals, erythrocytes typically contain greater than 70% of the organism’s iron in the form of heme in hemoglobin. Over the past several years, many of the transporter and accessory proteins involved in inter cellular iron metabolism have been described. However, many proteins involved in intra cellular iron metabolism beyond the basic components of the transferrin cycle remain elusive. Furthermore, the enzymatic components of heme biosynthesis are well characterized, but accessory transporters and other proteins required to shuttle heme precursors between mitochondria and the cytoplasm are unknown.
To investigate these areas, we are taking two general approaches. First we are positionally cloning and characterizing the genes underlying several mouse hereditary defects in erythroid iron and heme metabolism. Second, using targeted mutagenesis in the mouse, we are studying proteins implicated in the pathogenesis in a group of bone marrow disorders known as sideroblastic anemias,in which erythroid precursors develop pathologic mitochondrial iron deposits.
Rotation students are typically involved in physiological characterization and/or positional cloning of novel murine anemia phenotypes.
References:
- Ohgami RS, Campagna DR, Antiochos B, Wood EB, Sharp JJ, Barker JE, and Fleming MD. nm1054, a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse. Blood. 2005; Nov 15;106(10):3625-31.
- Ohgami R, Campagna D, Greer E, Antiochos B, McDonald A, Chen J, Sharp J, Fujiwara Y, Barker J, and Fleming, MD. Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nature Genetics. 2005; 37:1264-1269.
- Pondarré C, Antiochos BB, Campagna DR, Clarke SL, Greer EL, Deck KM, McDonald A, Han AP, Medlock A, Kutok JL, Anderson SA, Eisenstein RS, Fleming MD. The mitochondrial ATP-binding cassette transporter Abcb7 is essential in mice and participates in cytosolic iron-sulfur cluster biogenesis. Hum Mol Genet. 2006 Mar 15;15(6):953-64.
- Ohgami RS, Campagna DR, McDonald A, Fleming MD. The Steap proteins are metalloreductases. Blood. 2006 in press.
BBS webpage updated 12/02/2009

