Barry Paw, MD, PhD
|Hospital Title||Associate in Medicine|
|Academic Title||Associate Professor of Medicine|
Brigham & Women's Hospital
1 Blackfan Circle
Karp Research Bldg. 06.213
Boston, MA 02115
The focus of Barry Paw's laboratory research is studying genes important for red cell development using the zebrafish as a genetic 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, the Paw lab has undertaken forward genetic (mutagenesis) screens to isolate zebrafish mutants with defects in red cells. The genes disrupted in these mutants are then identified by a combination of positional and candidate cloning strategies as a way to gain insight into the genetic basis of vertebrate hematopoiesis.
Recently, his group has identified the gene disrupted in the frascati mutation as a novel mitochondrial metal transporter, Mitoferrin1 (Mfrn1, Slc25A37), crucial for red cell development. Loss of function of the Mitoferrin1 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 through evolution from yeasts to zebrafish and mammals. His group is now investigating the biochemical properties of the Mitoferrin transporter in red cell development in zebrafish, mouse, and cell culture models. His 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. Additional genes involved in mitochondrial iron and heme trafficking are being identified using proteomic and systems biology strategies in our group.
About Barry Paw
Dr. Paw received his A.B. (Biochemistry) degree from University of California, Berkeley, and his M.D. and Ph.D. (Biological Chemistry) degrees from University of California, Los Angeles School of Medicine. He completed an internship and residency in pediatrics at Boston Children's Hospital and a fellowship in pediatric hematology-oncology at Boston Children's Hospital and Dana-Farber Cancer Institute. He is currently an Associate Professor of Medicine at Harvard Medical School and an attending physician in Pediatric Oncology at Boston Children's Hospital and Dana-Farber Cancer Institute.
He was a recipient of the William Randolph Hearst Young Investigator Award in 2002, a Basil O'Connor Scholar Award from the March of Dimes Birth Defects Foundation in 2004, and the Young Investigator President's Award from the International BioIron Society in 2005. He was elected to the American Society for Clinical Investigation in 2008. His research group is funded by the March of Dimes Foundation and the National Institutes of Health (NHLBI and NIDDK).
For additional informational, please see Dr. Paw's specialist page.
Shaw GC, Cope JJ, Li L, Corson K, Hersey C, Wingert R, Ackermann GE, Gwynn B, Traver D, Trede NS, Barut BA, Minet E, Zhou Y, Donovan A, Brownlie A, Peters LL, Kaplan J, Zon LI, Paw BH. Mitoferrin is essential for erythroid iron assimilation. Nature 2006; 440: 96-100.
Nilsson R, Schultz IJ, Pierce EL, Soltis KA, Naranuntarat A, Ward DM, Baughman J, Paradkar PN, Kingsley PD, Culotta VC, Kaplan J, Palis J, Paw BH*, Mootha VK*. Discovery of genes essential for heme biosynthesis through large-scale gene expression analysis. Cell Metabolism 2009; 10:119-130. *[co-corresponding senior authors].
Chen W, Paradkar PN, Li L, Pierce EL, Langer NB, Takahashi-Makise N, Hyde BB, Shirihai OS, Ward DM, Kaplan J, Paw BH. Abcb10 physically interacts with mitoferrin1 (slc25a37) to enhance its stability and function in the erythroid mitochondria. Proc. Natl. Acad. Sci. USA 2009, 106:16263-16268.
Chen W, Dailey HA, Paw BH. Ferrochelatase forms an oligomeric complex with mitoferrin-1 and Abcb10 for erythroid heme biosynthesis. Blood 2010, 116:628-630.
Schultz IJ, Chen C, Paw BH*, Hamza I*. Iron and porphyrin trafficking in heme biogenesis. J. Biol. Chem. 2010, 285:26753-26759. *[co-corresponding senior authors].
Amigo JD, Yu M, Troadec MB, Gwynn B, Cooney JD, Lambert AJ, Chi NC, Weiss MJ, Peters LL, Kaplan J, Cantor AB, Paw BH. Identification of distal cis-regulatory elements at mouse mitoferrin loci using zebrafish transgenesis. Mol. Cell. Biol. 2011, 31:1344-1356.
- Wang Y, Langer NB, Shaw GC, Yang G, Li L, Kaplan J, Paw BH*, Bloomer JR*. Abnormal mitoferrin-1 expression in patients with erythropoietic protoporphyria. Exp. Hematol. 2011, 39:784-794. *[co-corresponding senior authors].