Jean Schaffer

Personal Information
Title Professor
Expertise Cardiovascular
Institution Washington University in St Louis
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Data Summary
Grants/SubContracts 2
Progress Reports 3
Presentations 1
Publications 10
Protocols 0
Committees 2

snoRNAs in Complications of Type 1 Diabetes
High circulating levels of metabolites cause diabetic complications through the generation of oxidative stress. We recently discovered that intronic small nucleolar RNAs (snoRNAs) play a critical role in metabolic and oxidative stress-induced cell death in cultured cells and animal models. Our data are the first to ascribe a function for snoRNAs in the regulatory networks of a pathophysiological response. Because these sequences are non-coding and often intronic, there is little data on variation in the snoRNAs in humans. In this project we will develop the methodology to systematically sequence human snoRNAs to understand the degree of conservation or variation. By comparing snoRNA sequences in diabetics with and without microvascular complications and in the publically available 1000 Genomes database, we will test the hypothesis that rare variation snoRNAs is associated with protection from diabetic complications.
The role of TLR-mediated inflammation in diabetic cardiomyopathy
Cardiovascular disease is the leading cause of death in diabetics who suffer from aggressive atherosclerosis and cardiomyopathy. Inflammation is now recognized as a central feature of obesity, insulin resistance, and diabetes. Nonetheless, the role of inflammatory pathways in the pathogenesis of diabetic cardiac dysfunction has been largely unexplored. Evidence is emerging that Toll-like receptor (TLR) 4 and 2, originally identified as host receptors for bacterial lipids and lipoproteins such as lipopolysaccharide (LPS), contribute to systemic insulin resistance in lipid overload states through a mechanism that may involve activation by saturated fatty acids. Our preliminary studies demonstrate alterations in myocardial lipid metabolism can activate inflammatory signaling in vivo. We will use mouse models of lipotoxic cardiomyopathy and diabetic cardiomyopathy combined with TLR4 and TLR2 loss of function to test the hypothesis that TLR-mediated inflammatory signaling contributes to the pathogenesis of diabetic cardiac dysfunction.

Progress Reports

Annual Reports
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Year: 2013; Items: 1

TLR4 activation under lipotoxic conditions leads to synergistic macrophage cell death through a TRIF-dependent pathway.
Schilling JD, Machkovech HM, He L, Diwan A, Schaffer JE
Journal of immunology (Baltimore, Md. : 1950), 2013 (190), 1285 - 1296

Year: 2012; Items: 2

Diabetic cardiovascular disease: getting to the heart of the matter.
Peterson LR, McKenzie CR, Schaffer JE
Journal of cardiovascular translational research, 2012 (5), 436 - 445
Macrophages modulate cardiac function in lipotoxic cardiomyopathy.
Schilling JD, Machkovech HM, Kim AH, Schwendener R, Schaffer JE
American journal of physiology. Heart and circulatory physiology, 2012 (303), H1366 - H1373

Year: 2011; Items: 1

Bayesian parameter estimation for characterizing the cyclic variation of echocardiographic backscatter to assess the hearts of asymptomatic type 2 diabetes mellitus subjects.
Anderson CC, Gibson AA, Schaffer JE, Peterson LR, Holland MR, Miller JG
Ultrasound in medicine & biology, 2011 (37), 805 - 812
Submitted Externally

Year: 2010; Items: 1

ApoA-1 in diabetes: damaged goods.
Ory DS, Schaffer JE
Diabetes, 2010 (59), 2358 - 2359

Year: 2009; Items: 5

Side chain oxygenated cholesterol regulates cellular cholesterol homeostasis through direct sterol-membrane interactions.
Gale SE, Westover EJ, Dudley N, Krishnan K, Merlin S, Scherrer DE, Han X, Zhai X, Brockman HL, Brown RE, Covey DF, Schaffer JE, Schlesinger P, Ory DS
The Journal of biological chemistry, 2009 (284), 1755 - 1764
Ca2+-independent alterations in diastolic sarcomere length and relaxation kinetics in a mouse model of lipotoxic diabetic cardiomyopathy.
Flagg TP, Cazorla O, Remedi MS, Haim TE, Tones MA, Bahinski A, Numann RE, Kovacs A, Schaffer JE, Nichols CG, Nerbonne JM
Circulation research, 2009 (104), 95 - 103
The non-coding RNA gadd7 is a regulator of lipid-induced oxidative and endoplasmic reticulum stress.
Brookheart RT, Michel CI, Listenberger LL, Ory DS, Schaffer JE
The Journal of biological chemistry, 2009 (284), 7446 - 7454
As a matter of fat.
Brookheart RT, Michel CI, Schaffer JE
Cell Metabolism, 2009 (10), 9 - 12
Quantitative analysis of the magnitude and time delay of cyclic variation of myocardial backscatter from asymptomatic type 2 diabetes mellitus subjects.
Gibson AA, Schaffer JE, Peterson LR, Bilhorn KR, Robert KM, Haider TA, Farmer MS, Holland MR, Miller JG
Ultrasound in medicine & biology, 2009 (35), 1458 - 1467
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Title YearTypeOptions
Schilling, Joel (2009 P&F)
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