Department of Regenerative Medicine and Cell biology

Research in Focus

Blood Sphingolipids in Homeostasis and Pathobiology

Sphingolipids have emerged as key signaling molecules involved in the regulation of a variety of cellular functions including cell differentiation, proliferation and death. Sphingolipids have been implicated in several diseases such as cancer, obesity, and atherosclerosis; however, efforts addressing blood sphingolipidomics are still limited. Sphingolipids in blood constitute part of the circulating lipoprotein particles (HDL, LDL and VLDL), carried by serum albumin and also present in blood cells and platelets. The development of methods to determine levels of circulating bioactive sphingolipids in humans and validation of these methods to be a routine clinical laboratory test could be a pioneering approach to diagnose disease in the population. This approach would probably evolve to be analogous in implication to determining "good" and "bad" cholesterol and triglyceride levels in lipoprotein classes.

Dr. Hammad’s group has established a profile of sphingolipids in “normal” human plasma and determined a reference range for circulating sphingolipid species to be used for translational research and clinical practices detecting disease biomarkers in both men and women. Analyses of plasma sphingolipids is performed by high performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC-MS/MS). The group reported altered sphingolipd profile in patients with post-traumatic stress disorder, in a lupus mouse model, and is currently working on several other collaborative studies in obesity, cancer, diabetes, and pre-eclampcia. The group also determined levels of sphingolipid species in isolated lipoprotein classes (HDL, LDL, and VLDL), showing that different plasma pools of sphingolipids may have different contributions to signaling in health and disease.

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Compositional analysis of total sphingolipid content in human plasma shows that sphingomyelin (SM) is the dominant sphingolipid. The sphingolipid composition in plasma is as follows: SM (87.7%) followed by lactosylceramide (LacCer, 5.8%), hexosylceramide (HexCer, 3.4%), ceramide (Cer, 2.8%), sphingosine 1-phosphate (S1P) and dihydrosphingosine 1-phosphate (dhS1P) (0.22%), ceramide 1-phosphate (Cer1P, 0.15%), and sphingosine (Sph) and dihydrosphingosine (dhSph, 0.005%).

posted 6/3/2013

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