Education:BS Zoology, Kuwait Univ.
MS Medical Parasitology, Univ. of London, UK
PhD Physiology, Pennsylvania State University
Postdoctoral Fellow, Medical University of South Carolina
The main focus of the Hammad laboratory has been on sphingolipid signaling mechanisms which mediate the survival of foam cells (lipid-laden macrophages) and their sustained cell activation in response to modified lipoproteins and lipoprotein-immune complexes. The transformation of macrophages into foam cells is a critical event in the development of atherosclerosis and defining mechanisms mediating foam cell formation and determining the role of foam cells in the pathology of atherosclerosis is an area of great clinical relevance. Our goal is to uncover targets in the signaling pathway such as receptors and/or sphingolipids that can have therapeutic implications for blocking cytokine release and prevention of vulnerable atherosclerotic plaques.
There are over 100 known autoimmune diseases, which are recognized singularly rather than in the overall category of autoimmunity. Few of the autoimmune diseases are Type 1 diabetes, lupus, rheumatoid arthritis, and antiphospholipid syndrome. Autoimmune diseases are characterized by the production of vast amounts of IgG’s that can form immune complexes. We showed that human monocytic cells phagocytose oxidized LDL immune complexes (oxLDL-IC) via the Fc-y receptor and transform into activated foam cells. We examined the effect of oxLDL-IC on sphingosine kinase 1 (SK1), an enzyme implicated in mediating pro-survival and inflammatory responses through the generation of the signaling molecule sphingosine-1-phosphate (S1P). Intriguingly, oxLDL-IC, but not oxLDL alone, induced an immediate translocation and release of SK1 into the conditioned medium. This finding indicates that S1P may be generated extracellularly in response to modified LDL immune complexes and may therefore promote cell survival and prolong cytokine release by activated macrophages. We also found that oxLDL-IC induced the formation and release of HSP70-containing and IL-1-containing exosomes via an acid sphingomyelinase-dependent mechanism. We aim to reveal specific targets in the signaling pathway that can have therapeutic implications for blocking cytokine release and to prevent formation and rupture of vulnerable atherosclerotic plaques develop under autoimmune conditions.
Another area of interest is the role of sphingolipids in blood as diagnostic and prognostic markers for disease processes. Sphingolipids 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. This approach would probably evolve to be analogous in implication to determining “good” and “bad” cholesterol, and triglyceride levels. Recently, we have demonstrated, prospectively, that decreased plasma levels of select ceramide species are associated with the development of macroalbuminuria in type 1 diabetes.
Another area of research is investigating the function of the holoparticle HDL receptor, Cubilin, in mediating uptake, degradation and transcytosis/exocytosis of HDL. Cubilin is expressed in the renal proximal tubule, intestine, and yolk sac endoderm. We aim to determine the physiological significance of cubilin-mediated renal uptake of filterable forms of HDL.
- Lee MH, Appleton KM, El-Shewy HM, Sorci-Thomas MG, Thomas MJ, Lopes-Virella MF, Luttrell LM, Hammad SM, Klein RL. S1P in HDL Promotes Interaction Between SR-BI and S1PR1 and Activates S1PR1-Mediated Biological Functions: Calcium Flux and S1PR1 Internalization. J Lipid Res. 2016, Nov 23. pii: jlr.M070706. [Abstract]
- Fu D, Yu JY, Yang S, Wu M, Hammad SM, Connell AR, Du M, Chen J, Lyons TJ. Survival or death: a dual role for autophagy in stress-induced pericyte loss in diabetic retinopathy. Diabetologia. 2016, Jul 30 [Abstract]
- Hammad SM, Baker NL, El Abiad JM, Spassieva SD, Pierce JS, Rembiesa B, Bielawski J, Lopes-Virella MF, Klein RL. Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study Neuromolecular Med. 2016, Jul 7 [Abstract]
- Iqbal J, Walsh MT, Hammad SM, Cuchel M, Tarugi P, Hegele RA, Davidson NO, Rader DJ, Klein RL, and Hussain MM. Microsomal Triglyceride Transfer Protein Transfers and Determines Plasma Concentrations of Ceramide and Sphingomyelin but Not Glycosylceramide. J Biol Chem. 2015; 290(43):25863-25875 [Abstract]
- Basu A, Yu JY, Jenkins AJ, Nankervis AJ, Hanssen KF, Henriksen T, Lorentzen B, Garg SK, Menard MK, Hammad SM, Scardo JA, Aston CE, and Lyons TJ. Trace elements as predictors of preeclampsia in type 1 diabetic pregnancy. Nutr Res. 2015; 35:421-430 [Abstract]
- Twal WO, Hammad SM, Guffy SL, and Argraves WS. A novel intracellular fibulin-1D variant binds to the cytoplasmic domain of integrin beta 1 subunit. Matrix Biol. 2015; 43:97-108 [Abstract]
- Al Gadban MM, Alwan MM, Smith KJ, and Hammad SM. Accelerated vascular disease in systemic lupus erythematosus: Role of macrophage. Clin Immunol. 2015; 157:133-144 [Abstract]
- Shrader S, Mauldin M, Hammad S, Mitcham M, and Blue A. Developing a comprehensive faculty development program to promote interprofessional education, practice and research at a free-standing academic health science center. J Interprof Care. 2015; 29(2):165-167 [Abstract]
- Klein RL*, Hammad SM*, Baker NL, Hunt KJ, Al Gadban MM, Cleary PA, Virella G, Lopes-Virella MF; DCCT/EDIC Research Group. Decreased plasma levels of select very long chain ceramide species are associated with the development of nephropathy in type 1 diabetes. Metabolism. 2014; 63:1287-1295 [Abstract]
- Du M, Basu A, Fu D, Wu M, Centola M, Jenkins AJ, Hanssen KF, Garg SK, Hammad SM, Scardo JA, Aston CE, and Lyons TJ. Serum inflammatory markers and preeclampsia in type 1 diabetes: a prospective study. Diabetes Care 2013; 36:2054-2961[Abstract]
- Hammad SM, Al Gadban MM, Semler AJ, Klein RL. Sphingosine 1-phosphate distribution in human plasma: associations with lipid profiles. J Lipids. 2012;2012:180705 [Abstract]
- Fu D, Wu M, Zhang J, Du M, Yang S, Hammad SM, Wilson K, Chen J, Lyons TJ. Mechanisms of modified LDL-induced pericyte loss and retinal injury in diabetic retinopathy. Diabetologia 2012; 55:3128-40 [Abstract]
- Yu Y., Hanssen K.F., Kalyanaraman V., Wilson K.W., Chirindel A., Jenkins A.J., Nankervis A.J., Torjesen P., Scholz H., Henriksen T., Lorentzen B., Garg S.K., Menard M.K., Hammad S.M., Scardo J.C., Stanley J.R., Wu M., Basu A., Aston C.E., and Lyons T.J., Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes preeclampsia in Type 1 diabetes. BJOG 2012; 119:1512-1520 [Abstract]
- Al Gadban M.M., German J., Truman J-P, Soodavar F., Riemer E.C., Twal W.O., Smith K.J., Heller D., Hofbauer A.F., Oates J.C., and Hammad S.M., Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus. Cellular Immunol. 2012 276:42-51 [Abstract]
- Hammad SM, Truman J-P, Al Gadban MM, Smith KJ, Twal WO, and Hamner MB. Altered blood sphingolipidomics and elevated plasma inflammatory cytokines in combat Veterans with post-traumatic stress disorder. Neurobiol Lipids Volume 10, Article 2 (2012) http://neurobiologyoflipids.org/content/10/2/
- Basu A, Alaupovic P, Wu M, Jenkins AJ, Yu Y, Nankervis AJ, Hanssen KF, Scholz H, Henriksen T, Lorentzen B, Clausen T, Garg SK, Menard MK, Hammad SM, Scardo JC, Stanley JR, Dashti A, Aston CE, and Lyons TJ. Plasma lipoproteins and pre-eclampsia in women with Type 1 diabetes: a prospective study. The Journal of Clinical Endocrinology & Metabolism 2012; 97:1752-1762. [Abstract]
- El-Shewy H.M., Sohn M., Wilson P., Hammad S.M., Luttrell L.M., and Jaffa A.A., Low-density lipoprotein induced expression of connective tissue growth factor via transactivation of sphingosine 1-phosphate receptors in mesangial cells. Molecular Endocrinology 2012; 26:833-845. [Abstract]
- Truman J-P, Al Gadban M.M., Smith K.J., Jenkins R.W., Mayroo N., Virella G., Lopes-Virella M.F., Bielawska A., Hannun Y.A., and Hammad S.M. Differential regulation of acid sphingomyelinase in monocytes stimulated with oxidized LDL and oxidized LDL immune complexes: role in phagocytosis and cytokine release. Immunology 2012; 136:30-45. [Abstract]
- Hammad SM. Blood sphingolipids in homeostasis and pathobiology. Adv Exp Med Biol. 2011 721:57-66. [Abstract]
- Azar M, Basu A, Jenkins AJ, Nankervis AJ, Hanssen KF, Scholz H, Henriksen T, Garg SK, Hammad SM, Scardo JA, Aston CE, Lyons TJ. Serum carotenoids and fat-soluble vitamins in women with type 1 diabetes and preeclampsia: a longitudinal study. Diabetes Care. 2011 Jun;34(6):1258-64. [Abstract]
- Truman JP, Al Gadban MM, Smith KJ, Hammad SM. Acid sphingomyelinase in macrophage biology. Cell Mol Life Sci. 2011 Oct;68(20):3293-305. Cover page [Abstract]
- Pilcher ES, Mauldin M, Hammad SM, McDougall C, Howell D. Interprofessional Faculty Development Institute: Empowering Leaders in Advanced Teambuilding. Journal of Dental Education. 2011 75(2):190-256.
- Al Gadban M.M., Smith K.J., Soodavar F., Piansay C., Chassereau C., Twal W.O., Klein R.L., Virella G., Lopes-Virella M.F., and Hammad S.M. Differential Trafficking of Oxidized LDL and Oxidized LDL Immune Complexes in Macrophages: Impact on Oxidative Stress. PLoS ONE 5 (2010): e12534. [Abstract]
- Hammad SM, Pierce JS, Soodavar F, Smith KJ, Al Gadban MM, Rembiesa B, Klein RL, Hannun YA, Bielawski J, Bielawska A. Blood sphingolipidomics in healthy humans: Impact of sample collection methodology. J Lipid Res. 2010; 51:3074-87. [Abstract]
- Lee MH*, Hammad SM*, Semler AJ, Luttrell LM, Lopes-Virella MF, Klein RL. HDL3, but not HDL2, stimulates plasminogen activator inhibitor-1 release from adipocytes: the role of sphingosine-1-phosphate. J Lipid Res. 2010; 51:2619-28. [Abstract]
- Smith KJ, Twal WO, Soodavar F, Virella G, Lopes-Virella MF, and Hammad, SM, HSP70B´ expression and release in response to human oxidized LDL immune complex in human monocytic cells. J Biol Chem. 2010;21;285(21):15985-93 [Abstract]
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