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David F. Bishop

David F.
Professor of Genetics and Genomic Sciences
Mount Sinai School of Medicine

The research interests of our laboratory are directed to an understanding of the molecular and medical genetics of heme biosynthesis and its regulation and control by the rate-limiting enzyme of the pathway, 5-aminolevulinate synthase (ALAS). Our discovery of the existence of erythroid and non-erythroid isozymes of ALAS, the cloning and sequencing of an erythroid tissue-specific gene, ALAS2, and its mapping to chromosome Xp11.21 led to our identification of ALAS2 as the defective gene in patients with X-linked sideroblastic anemia. Structure-function correlations between ALAS2 mutations found in X-linked sideroblastic anemia are being analyzed with the goals of diagnostic and therapeutic advances in the treatment of this genetic disorder.

Our laboratory is also interested in the development of tools for bioinformatics and has, in a collaborative project with the Department of Biostatistics, developed a set of computational algorithms that predicts putative functional regions of tissue-specific regulation in genomic sequences.

In collaboration with Dr. RJ Desnick, we are investigating approaches to gene therapy of the porphyrias using mouse models and studies into the reaction mechanism of uroporphyrinogen synthase and hydroxymethyl bilane synthase.

We are now initiating studies of the use of IPS Cells to treat a genetic disease (Congenital Erythropoietic Porphyria; CEP). These studies will use reprogrammed and corrected adult CEP skin cells from our mouse model of CEP as proof-of-principle for future treatment of human patients. These studies will compare murine and human iPS-derived cells with their ES cell counterparts at the mRNA and protein levels.

Select Publications: 

Scher W, Jing Y, Lu M, Bishop DF, Scher BM. Sequences of polycythemia-type Friend spleen focus-forming virus in clone-745-derived mouse erythroleukemia cells. Arch Virol. 2009;154(5):895-8.

Cunha L, Kuti M, Bishop DF, Mezei M, Zeng L, Zhou MM, Desnick RJ. Human uroporphyrinogen III synthase: NMR-based mapping of the active site. Proteins. 2008 May 1;71(2):855-73.

Yasuda M, Domaradzki ME, Armentano D, Cheng SH, Bishop DF, Desnick RJ. Acute intermittent porphyria: vector optimization for gene therapy. J Gene Med. 2007 Sep;9(9):806-11.

Bishop DF, Johansson A, Phelps R, Shady AA, Ramirez MC, Yasuda M, Caro A, Desnick RJ. Uroporphyrinogen III synthase knock-in mice have the human congenital erythropoietic porphyria phenotype, including the characteristic light-induced cutaneous lesions. Am J Hum Genet. 2006 Apr;78(4):645-58.

Chan P, Gonzalez-Maeso J, Ruf F, Bishop DF, Hof PR, Sealfon SC. Epsilon-sarcoglycan immunoreactivity and mRNA expression in mouse brain. J Comp Neurol. 2005 Jan 31;482(1):50-73.

Solis C, Martinez-Bermejo A, Naidich TP, Kaufmann WE, Astrin KH, Bishop DF, Desnick RJ. Acute intermittent porphyria: studies of the severe homozygous dominant disease provides insights into the neurologic attacks in acute porphyrias. Arch Neurol. 2004 Nov;61(11):1764-70.

Bekri S, May A, Cotter PD, Al-Sabah AI, Guo X, Masters GS, Bishop DF. A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia. Blood. 2003 Jul 15;102(2):698-704.

Cazzola M, May A, Bergamaschi G, Cerani P, Ferrillo S, Bishop DF. Absent phenotypic expression of X-linked sideroblastic anemia in one of 2 brothers with a novel ALAS2 mutation. Blood. 2002 Dec 1;100(12):4236-8.