Department of Regenerative Medicine and Cell biology

Samar Hammad

Samar M. Hammad, Ph.D.
Associate Professor


Office: Room 645, Basic Science Building (843) 876-5200
Lab: Room 645, Basic Science Building


Email: hammadsm@musc.edu

Education:

BS Zoology, Kuwait Univ.
MS Medical Parasitology, Univ. of London, UK
PhD Physiology, Pennsylvania State University
Postdoctoral Fellow, Medical University of South Carolina


Research Activity:

The Hammad laboratory is interested primarily in lipoprotein-related research.  Recently, our focus has been on investigating the 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.  Macrophages internalize oxidized LDL immune complexes (oxLDL-IC) via the Fc-y receptor and transform into activated foam cells.  Our data demonstrated that exposure of human monocytic cells to oxLDL-IC leads to increased cell survival compared to oxLDL alone.  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.  Our goal is to uncover mechanisms by which oxLDL-IC suppress apoptosis of foam cells, and reveal specific targets in the signaling pathway that can have therapeutic implications for blocking cytokine release and to prevent formation of vulnerable plaques.

Another area of interest is the role of modified lipoproteins in diabetic vascular complications including nephropathy.  We have investigated the effects of hypercholesterolemia on the development of diabetic complications in a genetically modified hypercholesterolemic mouse made diabetic with streptozotocin.  The mouse is a double knockout for the LDL receptor and the editing of the apoB mRNA (LDLr-/- Apobec -/-).  In this animal model, we found that the combination of hypercholesterolemia and diabetes resulted in a significant lipid accumulation in the tubular basement membrane, which could have contributed to the albuminuria.  We also published the first report on the mouse lipoprotein subclass profile using Nuclear Magnetic Resonance (NMR).

Another area of research, with which I am involved and collaborating with Dr. W.S. Argraves in the department, is the function of the newly discovered 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.  Our goal is to determine the physiological significance of cubilin-mediated renal uptake of filterable forms of HDL to HDL homeostasis.  A decreased level of plasma HDL is a major risk factor for coronary atherosclerosis.

Recent Publications:

  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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/
  7. 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]
  8. 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]
  9. 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]
  10. Hammad SM. Blood sphingolipids in homeostasis and pathobiology. Adv Exp Med Biol. 2011 721:57-66. [Abstract]
  11. 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]
  12. 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]
  13. 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.
  14. 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]
  15. 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]
  16. 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]
  17. 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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