Department of biochemistry and Molecular biology
L. Ashley Cowart, PhD
Biochemistry and Molecular Biology
2005 Research Health Scientist, Ralph H. Johnson VA Medical Center
2001-2005 Postdoctoral Fellowship, Dr. Yusuf Hannun, Biochemistry, MUSC
2001 Ph.D., Biochemistry, Vanderbilt University
1995 B.S., Biology, Furman University
Office: 512-D Basic Sciences Building
Lab: 513 Basic Sciences Building
Our laboratory studies how plasma lipids affect tissue sphingolipid metabolism. This is important because obesity and diabetes increase plasma lipid concentrations, and this increase has been demonstrated to change sphingolipid profiles in tissues including adipose, liver, skeletal muscle, and heart. In fact, elevation of plasma lipids probably contributes to pathologies observed in these tissues from diabetic patients. We hypothesize that aberrant sphingolipid synthesis promotes tissue pathologies including inflammation, muscle wasting, and cardiac hypertrophy. To address this hypothesis we use a combination of tissue culture and rodent models. Placing rodents on a high-fat diet increases plasma fatty acids and dramatically impacts tissue sphingolipids. These changes precipitate major changes in gene regulation and signaling pathways. We have dissected some of these changes using microarrays, and with collaborators in the department of Biostatistics, Bioinformatics, and Epidemiology, we also are actively developing novel bioinformatics strategies for co-analysis of gene expression data from microarrays and sphingolipid levels from lipidomics analysis. These strategies have allowed us to find “needles” in the “haystack” of lipid-mediated cell signaling.
Recent Publications | Additional Publications
Sutter AG, Palanisamy AP, Lench JH, Esckilsen S, Geng T, Lewin DN, Cowart LA, Chavin KD. (2015) Dietary Saturated Fat Promotes Development of Hepatic Inflammation through Toll-Like Receptor 4 in Mice. J Cell Biochem doi: 10.1002/jcb.25453. [Epub ahead of print]
Geng T, Sutter A, Harland MD, Law BA, Ross JS, Lewin D, Palanisamy A, Russo SB, Chavin KD, Cowart LA. (2015) SphK1 mediates hepatic inflammation in a mouse model of NASH induced by high saturated fat feeding and initiates proinflammatory signaling in hepatocytes. J Lipid Res 56(12):2359-71.
Geng T, Xia L, Russo S, Kamara D, Cowart LA. Prosteatotic genes are associated with unsaturated fat suppression of saturated fat-induced hepatic steatosis in C57BL/6 mice. (2015) Nutr Res 35(9):812-22.
Khakhina S, Johnson SS, Manoharlal R, Russo SB, Blugeon C, Lemoine S, Sunshine AB, Dunham MJ, Cowart LA, Devaux F, Moye-Rowley WS. (2015) Control of plasma membrane permeability by ABC transporters. Eukaryot Cell 14(5):442-53. PMID: 25724885
Jaishy B, Zhang Q, Chung HS, Riehle C, Soto J, Jenkins S, Abel P, Cowart LA, Van Eyk JE, Abel ED. (2015) Lipid-induced NOX2 activation inhibits autophagic flux by impairing lysosomal enzyme activity. J Lipid Res 56(3):546-61. PMID: 25529920
Rachidi S, Sun S, Wu BX, Jones E, Drake RR, Ogretmen B, Cowart LA, Clarke CJ, Hannun YA, Chiosis G, Liu B, Li Z. (2015) Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis. J Hepatol 62(4):879-88. PMID: 25463537
Jin J, Zhang X, Lu Z, Perry DM, Li Y, Russo SB, Cowart LA, Hannun YA, Huang Y. (2013) Acid sphingomyelinase plays a key role in palmitic acid-amplified inflammatory signaling triggered by lipopolysaccharide at low concentrations in macrophages. Am J Physiol Endocrinol Metab 305(7):E853-67. PMID: 23921144
Geng T, Hu W, Broadwater MH, Snider JM, Bielawski J, Russo SB, Schwacke JH, Ross J, Cowart LA. (2013) Fatty acids differentially regulate insulin resistance through endoplasm reticulum stress-mediated induction of tribbles homologue 3: a potential link between dietary fat composition and the pathophysiological outcomes of obesity. Diabetologia 56(9):2078-87.
Ross JS, Hu W, Rosen B, Snider AJ, Obeid LM, Cowart LA. (2013) Sphingosine kinase 1 is regulated by peroxisome proliferator-activated receptor α in response to free fatty acids and is essential for skeletal muscle interleukin-6 production and signaling in diet-induced obesity. J Biol Chem 288(31):22193-206.
Russo SB, Ross JS, Cowart LA. (2013) Sphingolipids in obesity, type 2 diabetes, and metabolic disease. Handb Exp Pharmacol (216):373-401. Review.
Russo SB, Tidhar R, Futerman AH, Cowart LA. (2013) Myristate-derived d16:0 sphingolipids constitute a cardiac sphingolipid pool with distinct synthetic routes and functional properties. J Biol Chem 288(19):13397-409.
Russo SB, Baicu CF, Van Laer A, Geng T, Kasiganesan H, Zile MR, Cowart LA. (2012) Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes. J Clin Invest 122(11):3919-30.
Montefusco DJ, Newcomb B, Gandy JL, Brice SE, Matmati N, Cowart LA, Hannun YA. (2012) Sphingoid bases and the serine catabolic enzyme CHA1 define a novel feedforward/feedback mechanism in the response to serine availability. J Biol Chem 287(12):9280-9.
Brice SE, Cowart LA. (2011) Sphingolipid metabolism and analysis in metabolic disease. Adv Exp Med Biol 721:1-17. Review. PMID: 21910079c
Hu W, Ross J, Geng T, Brice SE, Cowart LA. (2011) Differential regulation of dihydroceramide desaturase by palmitate versus monounsaturated fatty acids: implications for insulin resistance. J Biol Chem 286(19):16596-605. PMID: 2145453
Johnson SS, Hanson PK, Manoharlal R, Brice SE, Cowart LA, Moye-Rowley WS. (2010) Regulation of yeast nutrient permease endocytosis by ATP-binding cassette transporters and a seven-transmembrane protein, RSB1. J Biol Chem 285(46):35792-802. PMID: 20826817
Cowart LA, Gandy JL, Tholanikunnel B, Hannun YA. (2010) Sphingolipids mediate formation of mRNA processing bodies during the heat-stress response of Saccharomyces cerevisiae. Biochem J 431(1):31-8. PMID: 20629639
Cowart LA. (2010) A novel role for sphingolipid metabolism in oxidant-mediated skeletal muscle fatigue. Focus on "Sphingomyelinase stimulates oxidant signaling to weaken skeletal muscle and promote fatigue". Am J Physiol Cell Physiol 299(3):C549-51. PMID: 2057399
Richards AJ, Muller B, Shotwell M, Cowart LA, Rohrer B, Lu X. (2010) Assessing the functional coherence of gene sets with metrics based on the Gene Ontology graph. Bioinformatics 26(12):i79-87. PMID: 20529941
Cowart LA, Shotwell M, Worley ML, Richards AJ, Montefusco DJ, Hannun YA, Lu X. (2010) Revealing a signaling role of phytosphingosine-1-phosphate in yeast. Mol Syst Biol 6:349. PMID: 20160710
Hu W, Bielawski J, Samad F, Merrill AH Jr, Cowart LA. (2009) Palmitate increases sphingosine-1-phosphate in C2C12 myotubes via upregulation of sphingosine kinase message and activity. J Lipid Res 50(9):1852-62. PMID: 19369694
Kitagaki H, Cowart LA, Matmati N, Montefusco D, Gandy J, de Avalos SV, Novgorodov SA, Zheng J, Obeid LM, Hannun YA. (2009) ISC1-dependent metabolic adaptation reveals an indispensable role for mitochondria in induction of nuclear genes during the diauxic shift in Saccharomyces cerevisiae. J Biol Chem 284(16):10818-30. PMID: 19179331
Brice SE, Alford CW, Cowart LA. (2009) Modulation of sphingolipid metabolism by the phosphatidylinositol-4-phosphate phosphatase Sac1p through regulation of phosphatidylinositol in Saccharomyces cerevisiae. J Biol Chem 284(12):7588-96. PMID: 19139096