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Department
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Hematology/Oncology
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Hospital Title
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Assistant in Medicine
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Academic Title
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Assistant Professor of Medicine
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Phone
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617-355-9008; 617-632-4924
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Fax
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617-355-9064
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Email
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Barry Paw
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Location
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Brigham & Women's Hospital
Division, Hematology
1 Blackfan Circle
Karp Research Bldg. 06.213
Boston, MA 02115
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The focus of Barry Paw's laboratory research is studying genes important for red cell and platelet 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 and thrombocytes (platelet-equivalent). 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, Mitoferrin (Mfrn, Slc25A37), crucial for red cell development. 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 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.
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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 Children's Hospital Boston and a fellowship in pediatric hematology-oncology at Children's Hospital Boston and Dana-Farber Cancer Institute. He is currently an Assistant Professor of Medicine at Harvard Medical School and an attending physician in Pediatric Oncology at Children's Hospital Boston 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).
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- Paw BH, Davidson AJ, Zhou Y, Li R, Pratt SJ, Lee C, Trede NS, Brownlie A, Donovan A, Liao EC, Ziai JM, Drejer AH, Guo W, Kim CH, Gwynn B, Peters LL, Chernova MN, Alper SL, Zapata A, Wickramasinghe SN, Lee MJ, Lux SE, Fritz A, Postlethwait JH, Zon LI. Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency. Nature Genetics 2003; 34: 59-64.
- Ackermann GE, Paw BH. Zebrafish: genetic model for vertebrate organogenesis and human disorders. Frontiers in Bioscience 2003; 8: d1227-1253
- Shafizadeh E, Paw BH. Zebrafish as a model for human hematologic disorders. Current Opinion in Hematology 2004; 11: 255-261.
- 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.
- Dore LC, Amigo JD, dos Santos CO, Zhang Z, Gai X, Tobias JW, Yu D, Dorman C, Wu W, Hardison RC, Paw BH*, Weiss MJ*. A GATA-1 regulated microRNA locus essential for erythropoiesis. Proc. Natl. Acad. Sci. USA 2008; in press [*co-corresponding senior authors].
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