Jean E. Schaffer, M.D.

Professor
Internal Medicine
Cardiology
Developmental Biology

Molecular Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-362-8717

  • 314-362-8937

  • 314-747-0264

  • 8086

  • BJC-IH 10401

  • jschaff@wustl.edu

  • http://schafferlab.wustl.edu/

  • metabolism, RNA, cell death, diabetes, heart disease

  • Cellular responses to metabolic stress

Research Abstract:

Our lab uses genetic, biochemical, cell biological, and physiological approaches to study mechanisms through which metabolic stress leads to cell dysfunction and cell death. A major area of focus is the lipotoxicity that results from high circulating free fatty acids and triglycerides, metabolic abnormalities that are common in type 2 diabetes and that contribute to complications in the heart, the liver, and other tissues. We have developed mouse models of diabetic cardiomyopathy, characterized alterations in cellular lipid metabolism using sensitive mass spectrometry based approaches, and carried out genetic screens to delineate the molecular underpinnings of the response to lipotoxic stress. Currently the lab is studying non-canonical functions of small nucleolar RNAs (snoRNAs), regulated RNA degradation, and translational regulation in response to metabolic stress. Other areas of interest are post-lysosomal cholesterol trafficking networks and disruption of these pathway in inherited disorders of cholesterol metabolism.

Selected Publications:

Rimer JM, Lee, J, Holley CH, Chen DL, Hanson, PI, Ory, DS, Schaffer, JE. Long-range function of secreted small nucleolar RNAs that direct 2-O-methylation. J Biol Chem, 2018 Jul 6. pii: jbc.RA118.003410. doi: 10.1074/jbc.RA118.003410. [Epub ahead of print]


Lee J, Harris AN, Holley CL, Mahadevan J, Pyles KD, Lavagnino Z, Scherer DE, Fujiwara H, Sidhu R, Zhang J, Huang SCC, Piston DW, Remedi MS, Urano F, Ory DS, Schaffer JE. Rpl13a small nucleolar RNAs regulate systemic glucose metabolism. J Clin Invest 2016, in press

Caputa G, Zhao S, Guerrero AE, Ory DS, Duncan JG, Schaffer JE. RNASET2 is required for oxidative stress-mediated cell death. Cell Death & Differentiation, 2015, 23:347-357. PMCID: PMC4716297

Jinn S, Brandis KA, Ren, A, Chacko A, Dudley-Rucker N, Fujiwara H, Jiang H, Olsen BN, Schaffer JE, and Ory DS. snoRNA U17 regulates cellular cholesterol trafficking. Cell Metab 2015, 21: 855-867. PMCID: PMC4456254

Holley CL, Li MW, Scruggs BS, Matkovich SJ, Ory DS, Schaffer JE. Cytoplasmic snoRNAs are dynamically regulated by NADPH oxidase. J Biol Chem 2015, 290: 11741-11748. PMCID: PMC4416874

Schilling J, Machkovech H, Kim AHJ, Schwendener R, Schaffer JE. Macrophages modulate cardiac function in lipotoxic cardiomyopathy. Am J Physiol 2012, 303: H1366-H1373. PMCID: PMC3532539

Michel CI, Holley, CL, Scruggs BS, Sidhu, R, Brookheart RT, Listenberger LL, Behlke M, Ory DS, Schaffer JE. Small nucleolar RNAs, U32, U33, and U35 are critical mediators of metabolic stress. Cell Metab 2011, 14: 33-44. PMCID: PMC3138526

Borradaile NM, Buhman KK, Listenberger LL, Magee CJ, Morimoto TA, Ory DS, Schaffer JE. A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death. Mol Biol Cell 2006 17:770-778.

Listenberger LL, Han X, Lewis SL, Cases S, Farese RV, Ory DS, Schaffer JE. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci USA 2003 100:3077-3082.

Chiu H-C, Kovacs A, Ford DA, Hsu F-F, Garcia R, Herrero P, Saffitz JE, Schaffer JE. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest 2001 107:813-822.

Last Updated: 7/27/2018 11:12:06 AM

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