Michael Schlame

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Michael Schlame

Associate Professor, Department of Anesthesiology, Perioperative Care, and Pain Medicine
Associate Professor, Department of Cell Biology

Director Cardiac Anesthesia NYU Anesthesia Associates
NYU Critical Care Associates

Contact Info

Address
560 First Avenue
New York, NY 10016

Education

1985-1989 — Humboldt University - Berlin, Residency Training
2002-2004 — NYU School of Medicine, Residency Training

Research Summary

Barth syndrome is a hereditary cardiomyopathy that also affects skeletal muscles, growth, and neutrophils. The mutated gene (tafazzin) is homologous to a conserved family of phospholipid acyltransferases. Children with Barth syndrome are deficient in the mitochondrial phospholipid cardiolipin, suggesting that the primary defect of the disease may indeed be found in phospholipid metabolism and may specifically affect the phospholipids of mitochondria. We want to study the mechanism by which tafazzin mutation causes cardiomyopathy and skeletal muscle disease. First, we want to identify the enzymatic function of tafazzin. We will identify the intracellular localization of tafazzin, its impact on lipid composition, and its mechanism of action. Second, we want to examine the effect of tafazzin on structure and function of mitochondria. Since mitochondrial dysfunction is a plausible etiology of cardiomyopathy and skeletal muscle weakness, we will analyze mitochondrial ultrastructure and oxidative phosphorylation in cell lines with tafazzin deletion. Third, we want to explore a Drosophila model of Barth syndrome, which was created in our laboratory. We will study lipid metabolism, muscle physiology, morphology, and mitochondrial ultrastructure in fruit flies with tafazzin deletion. The Drosophila model will also be used for cardiac studies since flies contain a contractile fluid pumping organ that shares conserved features of cardiogenesis with all heart-forming creatures, including humans. The project will provide insight into the pathologic mechanism of a unique disease, which presents a novel pathway from lipid defect(s) to cardio-skeletal myopathy. Such information may be useful for the development of new therapeutic approaches to cardiomyopathy and skeletal muscle disease.

Research Interests

Cardiomyopathy, Lipid Biochemistry and Mitochondria.

Cardiolipin as key lipid of mitochondria in health and disease. 2nd Edition, Florence, Italy, September 30-October 1, 2015
Corcelli, Angela; Schlame, Michael. Cardiolipin as key lipid of mitochondria in health and disease. 2nd Edition, Florence, Italy, September 30-October 1, 2015. Chemistry & physics of lipids. 2016 Apr 27;198:10-12 (2101012)

Biosynthesis, remodeling and turnover of mitochondrial cardiolipin
Schlame, Michael; Greenberg, Miriam L. Biosynthesis, remodeling and turnover of mitochondrial cardiolipin. Biochimica & biophysica acta. 2016 Aug 21;:?-? (2221542)

Loss of protein association causes cardiolipin degradation in Barth syndrome
Xu, Yang; Phoon, Colin K L; Berno, Bob; D'Souza, Kenneth; Hoedt, Esthelle; Zhang, Guoan; Neubert, Thomas A; Epand, Richard M; Ren, Mindong; Schlame, Michael. Loss of protein association causes cardiolipin degradation in Barth syndrome. Nature chemical biology. 2016 Jun 27;12(8):641-647 (2166952)

Tafazzins from Drosophila and mammalian cells assemble in large protein complexes with a short half-life
Xu, Yang; Malhotra, Ashim; Claypool, Steven M; Ren, Mindong; Schlame, Michael. Tafazzins from Drosophila and mammalian cells assemble in large protein complexes with a short half-life. Mitochondrion. 2015 Jan 15;21:27-32 (1439892)

Membrane curvature modulation of protein activity determined by NMR
Epand, Richard M; D'Souza, Kenneth; Berno, Bob; Schlame, Michael. Membrane curvature modulation of protein activity determined by NMR. Biochimica & biophysica acta. 2014 May 13;1848(1 Pt B):220-228 (1003462)