BBS Faculty Member - Barry Paw

Barry Paw

Department of Medicine
Division, Hematology

Brigham and Women's Hospital
Karp Research Building Room 05.211
1 Blackfan Circle
Boston, MA 02115
Tel: 617-355-9008
Fax: 617-355-9064
Email: bpaw@rics.bwh.harvard.edu
Lab Members: 6 postdoctoral fellows, 1 medical resident, 1 technician
Visit my lab page here.



Genetics of Blood Cell Development
The focus of our 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, our lab has undertaken 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. 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
Recently, our 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. Our group is now investigating the biochemical properties of the Mitoferrin transporter in red cell development 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.









Last Update: 1/15/2014



Publications

For a complete listing of publications click here.

 


 

Shaw GC, Cope JJ, Li L, Corson K, Hersey C, Ackermann GE, Gwynn B, Lambert AJ, Traver D, Trede NS, Barut BA, Minet E, Zhou Y, Donovan A, Brownlie A, Balzan R, Weiss MJ, Peters LL, Kaplan J, Zon LI, Paw BH. Mitoferrin is essential for erythroid iron assimilation. Nature (2006) 440:96-100.

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.

Shah DI, Takahashi-Makise N, Cooney JD, Li L, Schultz IJ, Pierce EL, Narla A, Seguin A, Hattangadi SM, Medlock A, Langer NB, Dailey TA, Hurst SN, Faccenda D, Wiwczar J, Heggers SK, Vogin G, Chen W, Chen C, Campagna DR, Brugnara C, Zhou Y, Ebert BL, Danial NN, Fleming MD, Ward DM, Campanella M, Dailey HA, Kaplan J,
Paw BH. Mitochondrial Atpif1 regulates heme synthesis in developing erythroblasts. Nature (2012) 491:608-612.

Chen C, Garcia-Santos D, Ishikawa Y, Seguin A, Li L, Fegan KH, Hildick-Smith GJ, Shah DI, Cooney JD, Chen W, King MJ, Yien YY, Schultz IJ, Anderson H, Dalton AJ, Freedman ML, Kingsley PD, Palis J, Hattangadi SM, Lodish HF, Ward DM, Kaplan J, Maeda T, Ponka P,
Paw BH. Snx3 regulates recycling of the transferrin receptor and iron assimilation. Cell Metabolism (2013) 17:343-352.

Hildick-Smith GJ, Cooney JD, Garone C, Kremer L, Haack TB, Thon JN, Miyata N, Lieber DS, Calvo SE, Akman HO, Yien YY, Huston NC, Branco DS, Shah DI, Freedman ML, Koehler CM, Italiano JE, Merkenschlager A, Beblo S, Strom TM, Meitinger T, Freisinger P, Donati MA, Prokisch H, Mootha VK, DiMauro S,
Paw BH. Macrocytic anemia and mitochondriopathy resulting from a defect in Sideroflexin 4. Am. J. Hum. Genet. (2013) 93:906-914.



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