Nancy Braverman, MD, M.Sc.

Primary Axis: 
Medical Genetics and Genomics
Email: 
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Research Focus: 

We are studying the peroxisome biogenesis disorders (PBD), a heterogeneous group of inherited metabolic disorders associated with the failure to form functional peroxisomes. This results in multiple enzyme deficiencies and mutisystem, progressive diseases of childhood. Clinical features include bone, eye liver and kidney abnormalities, neuronal migration defects and mental retardation. The PBD provide a unique example of defects in biochemical pathways causing developmental abnormalities. These pathways are involved in complex lipid metabolism, for example, the committing steps of ether phospholipid synthesis, a specialized class of membrane lipids, are in the peroxisome. We study genotype-phenotype correlations in patients with these disorders. We have generated murine models to study the pathophysiology of one, PEX7 deficiency, which features loss of ether phospholipids. Finally, we have begun several cell-based projects to identify metabolic and molecular based therapies for these diseases.

External Website: 
External Website
Keywords: 
Peroxisome Biogenesis Disorders, Gene Structure and Function, Genotype-Phenotype Correlations, Animal Models, Metabolism, Drug Screening, Translational Research
Publications:
Wood PL, Khan MA, Smith T, Ehrmantraut G, Jin W, Cui W, Braverman NE, Goodenowe DB. In vitro and in vivo plasmalogen replacement evaluations in rhizomelic chrondrodysplasia punctata and Pelizaeus-Merzbacher disease using PPI-1011, an ether lipid plasmalogen precursor. Lipids Health Dis. (1):182. [Epub ahead of print]; 18 Oct 2011
Itzkovitz B, Jiralerspong S, Nimmo G, Loscalzo M, Horovitz DD, Snowden A, Moser A, Steinberg S, Braverman N. Functional characterization of novel mutations in GNPAT and AGPS, causing Rhizomelic Chondrodysplasia Punctata (RCDP) types 2 and 3. Hum Mutat. doi: 10.1002/humu.21623. [Epub ahead of print]; 11 Oct 2011
Alfares A, Dempsey Nunez L, Al-Thihli K, Mitchell J, Melancon S, Anastasio N, C H Ha K, Majewski J, Rosenblatt DS, and Braverman N. Combined malonic and methylmalonic aciduria: exome sequencing reveals mutations in the ACSF3 gene in patients with a non-classic phenotype. JMG Online First, published as 10.1136/jmedgenet-2011-100230; 23 July 2011
Sébastien Lévesque, Marie Lambert, Aspasia Karalis, Serge Melancon, Laura Russell and Nancy Braverman. Short term outcome of propionic aciduria treated at presentation with N-Carbamylglutamate: a retrospective review of four patients. Accepted Journal of Inherited Metabolic Disease; April 2011
Dranchak PK, Di Pietro E, Snowden A, Oesch N, Braverman NE, Steinberg SJ, Hacia JG. Nonsense suppressor therapies rescue peroxisome lipid metabolism and assembly in cells from patients with specific PEX gene mutations. J Cell Biochem; 28 Dec 2010
Kronn D, Mofidi S, Braverman N, Harris K; Diagnostics Guidelines Work Group. Diagnostic guidelines for newborns who screen positive in newborn screening. Genet Med. 12(12 Suppl):S251-5; Dec 2010
Nimmo G, Monsonego S, Descartes M, Franklin J, Steinberg S, Braverman N. Rhizomelic chrondrodysplasia punctata type 2 resulting from paternal isodisomy of chromosome 1. Am J Med Genet A. 152A(7):1812-7; 2010
Zhang R, Chen L, Jiralerspong S, Snowden A, Steinberg S, Braverman N. Recovery of PEX1-Gly843Asp peroxisome dysfunction by small-molecule compounds. Proc Natl Acad Sci U S A. 107(12):5569-74; 2010
Phadke SR, Gupta N, Girisha K M, Kabra M, Maeda M, Vidal E, Moser A, Steinberg S, Puri RD, Verma IC, Braverman N. Rhizomelic chondrodysplasia punctata type 1: report of mutations in 3 children from India. Appl Genet. 51(1):107-10; 2010
Braverman N, Zhang R, Chen L, Nimmo G, Scheper S, Tran T, Chaudhury R, Moser A, Steinberg S. A Pex7 hypomorphic mouse model for plasmalogen deficiency affecting the lens and skeleton. Mol Genet Metab. 99(4):408-16; 2010