Office: 843-792-0755
Lab: 843-792-0755
Fax: 843-792-4850
Email: szulcz@musc.edu
BSB-748

Research Interests

My research is focused on understanding how sphingolipids (SPLs) act on the molecular level in cell. Although rich diversity of SPLs structure correlates well with their critical and multiple roles in the regulation of many cellular functions and structural features of cell membrane, there is still insufficient level of knowledge of how they interact with the target proteins and receptors. In order to investigate these topics the rational design and synthesis of diversified library of SPL.s and their analogs as molecular probes and research reagents to study lipid-protein interactions are our goals.

Specifically, I am developing synthetic methods to introduce specific label, substituent or group into distinct sites in different locations in SPLs structure to modify their biological activity as well as to improve water solubility, efficient cellular delivery and specific targeting to sites/organelles where active protein targets may be present. The accompanying figure illustrates the key four sites of specific chemical modifications in ceramide structure which can be used to tune its properties and generate potent enzyme functions regulators or novel anticancer therapeutics.

Selected Publications

• Liu, X., Elojeimy, S., Turner, L.S., Mahdy, A.E., Zeidan, Y.H., Bielawska, A., Bielawski, J., Dong, J.Y., El-Zawahry, A.M., Guo, G.W., Hannum, Y.A., Holman, D.H., Rubinchik, S., Szulc, Z., Keane, T.E., Tavasolli, M. and Norris, J.S. (2008) Acid ceramidase inhibition: a novel target for cancer therapy. Front Biosci., 13: 2293-2298.
• Szulc, Z.M., Mayroo, N., Bai, A., Bielawski, J., Norris, J., Hannun, Y.A. and Bielawska, A. (2008) Novel analogs of D-e-MAPP and B13. Part 1. Synthesis and evaluation as potential anticancer agents. Bioorg. Med. Chem., 16 : 1015-1031.
• Bielawska, A., Bielawski, J., Szulc, Z.M., Mayroo, N., Liu, X., Bai, A. Elojeimy, S., Rembiesa, B., Pierce, J., Norris, J. and Hannun, Y.A. (2008) Novel analogs of D-e-MAPP and B13. Part 2. Signature effects on bioactive sphingolipids. Bioorg. Med. Chem., 16 : 1032-1045.
• Sun, W., Xu, R., Hu, W., Jin, J., Crellin, H.A., Bielawski, J., Szulc, Z.M., Thiers, B.H., Obeid, L.M. and Mao, C. (2008) Upregulation of the human alkaline ceramidase 1 and acid ceramidase mediates calcium-induced differentiation of epidermal keratinocytes. J. Invest. Dermatol., 128:389-397.
• Dahm, F., Bielawska, A., Nocito, A., Georgiev, P., Szulc, Z.M., Bielawski, J., Jochum, W., Dindo, D., Hannun, Y.A. and Clavien, P.A. (2008) Mitochondrially targeted ceramide LCL-30 inhibits colorectal cancer in mice. Br. J. Cancer, 98: 98-105.
• Holman, D.H., Turner, L.S., El-Zawahry, A., Elojeimy, S., Liu, X., Bielawski, J., Szulc, Z.M., Norris, K., Zeidan, Y.H., Hannun, Y.A., Bielawska, A. and Norris, J.S. (2008) Lysosomotropic acid ceramidase inhibitor induces apoptosis in prostate cancer cells. Cancer Chemother. Pharmacol., 61: 231-242.
• Szulc, Z.M., Obeid, L.M., Hannun, Y.A. and Bielawska, A. (2007) Highly efficient and regioselective phosphorylation of sphingolipids by phase-transfer catalysis. Polish J. Chem., 81: 1899-1909.
• Kraveka, J.M., Li, L., Szulc, Z.M., Bielawski, J., Ogretmen, B., Hannun, Y.A., Obeid, L.M. and Bielawska, A. (2007) Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cell. J. Biol. Chem., 282: 16718-16728.
• Xu, R., Jin, J., Hu, W., Sun, W., Bielawski, J., Szulc, Z., Taha, T., Obeid, L.M. and Mao C. (2006) Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P. FASEB J., 20: 1813-1825.
• Liu, X., Zeidan, Y.H., Elojeimy, S., Holman, D.H., El-Zawahry, A.M., Guo, G.W., Bielawska, A., Bielawski, J., Szulc, Z., Rubinchik, S., Dong, J.Y., Keane, T.E., Tavassoli, M., Hannun, Y.A. and Norris, J.S. (2006) Involvement of sphingolipids in apoptin-induced cell killing. Mol. Ther., 14: 627-636.
• Bielawski, J., Szulc, Z.M., Hannun, Y.A. and Bielawska, A. (2006) Simultanous quantitative analysis of bioactive sphingolipids by high performance liquid chromatography-tandem mass spectrometry, Methods, 39: 82-91.
• Senkal, C., Ponnusamy, S., Rossi, M., Sundaraj, K., Szulc, Z.M., Bielawski, J., Bielawska, A., Meyer, M., Cobanoglu, B., Koybasi, S., Sinha, D., Day, T., Obeid, L.M., Hannun, Y.A. and Ogretmen B. (2006) Potent anti-tumor activity of a novel cationic pyridinium-ceramide alone or in combination with gemcitabine against human head and neck squamous cell carcinomas in vitro and in vivo. J. Pharmacol. Exp. Ther., 317: 1188-1199.
• Szulc, Z.M., Bielawski, J., Gracz, H., Gustilo, M., Mayroo, N., Hannun, Y.A., Obeid L.M. and Bielawska, A. (2006) Tailoring structure-function and targeting properties of ceramides by site-specific cationization. Bioorg. Med. Chem., 14: 7083-7104.
• Dindo, D., Dahm F., Szulc Z., Bielawska A., Obeid, L.M., Hannun, Y.A., Graf, R. and Clavien PA. (2006) Cationic long-chain ceramide analog LCL30 induces cell death by mitochondrial targeting in SW 403 cells. Mol. Cancer Ther., 5: 1520-1529.
• Sultan, I., Senkal, C.E., Ponnusamy, S., Bielawski, J., Szulc, Z., Bielawska, A., Hannun Y.A. and Ogretmen, B. (2005) Regulation of the sphingosine recycling pathway for ceramide by oxidative stress, and its role incontrolling c-Myc/Max function. Biochem. J. 393: 513-521.
• Wijesinghe, D.S., Massiello, A., Subramanian, P., Szulc, Z., Bielawska, A., Chalfant, C.E. (2005) Substrate specificity of human ceramide kinase. J. Lipid Res., 46: 2706-2716
• Subramanian, P., Stahelin, R.V., Szulc, Z., Bielawska, A., Cho, W., Chalfant, C.E. (2005) Ceramide 1-phosphate acts as a positive allosteric activator of group IVA cytosolic phospholipase A2 {alpha} and enhances the interaction of the enzyme with phosphatidylcholine. J. Biol. Chem., 280: 17601-17607.
• Novgorodov, S.A., Szulc, Z.M., Luberto, C., Jones, J.A., Bielawski, J., Bielawska, A., Hannun, Y.A. and Obeid, L.M. (2005) Positively charged ceramide is a potent inducer of mitochondrial permeabilization. J. Biol Chem.; 280: 16096-16105.
• Hu, W., Xu, R., Zhang, G., Jin, J., Szulc, Z.M., Bielawski, J., Hannun, Y.A., Obeid, L.M. and Mao, C. (2005) Golgi fragmentation is associated with ceramide-induced cellular effects. Mol. Biol. Cell., 16: 1555-1567.
• Rossi, M.J., Sundararaj, K., Koybasi, S., Phillips, M.S., Szulc, Z.M., Bielawska, A., Day, T.A., Obeid, L.M., Hannun, Y.A. and Ogretmen, B. (2005) Inhibition of growth and telomerase activity by novel cationic ceramide analogs with high solubility in human head and neck squamous cell carcinoma cells. Otolaryngol. Head Neck Surg., 2: 55-62.
• Usta, J., El-Bawab, S., Roddy, P., Szulc, Z., Hannun, Y.A. and Bielawska, A. (2001) Structural Requirements of Ceramide and Sphingosine Based Inhibitors of Mitochondrial Ceramidase. Biochemistry, 40(32): 9657-9668.
• El-Bawab, S., Usta, J., Roddy, P., Szulc, Z., Bielawska, A. and Hannun, Y.A. (2001) Substrate specificity of Mitochondrial Ceramidase. J. Lipid Res. 43(1):141-148.
• Mao, C., Xu, R., Szulc, Z.., Bielawska, A., Galadari, S.H., Obeid, L.M. (2001) Cloning and Characterization of a Novel Human Alkaline Cermidase. A Mammalian enzyme that hydrolyzes phytoceramide. J. Biol. Chem., 276(28): 26577-26588.
• ElBawab, S., Birbes, H., Roddy, P., Szulc, Z.., Bielawska, A., and Hannun, Y.A. (2001) Biochemical characterization of the reverse activity of rat brain ceramidase. A CoA-dependent and fumonisin B1-insensitive ceramide synthase. J. Biol. Chem., 276(20): 16758-16766.
• Szulc, Z., Hannun, Y.A., and Bielawska, A. (2000) A Facile Regioselective Synthesis of sphingosine-1-Phosphate and Ceramide-1-Phosphate. Tetrahedron Letters 41: 7821-7824
• Mao, C., Xu, R., Bielawska, A., Szulc, Z.. and Obeid, L.M. (2000) Cloning and characterization of a Saccharomyces cerevisiae alkaline ceramidase with specificity for dihydroceramide. J. Biol. Chem., 275(40): 31369-31378.
• Bielawska, A, Hannun, YA, Szulc, Z. (2000) Radiolabeled Sphingolipids, Part I. Radiolabeling in the Sphingolipid Backbone. Methods in Enzymology: Sphingolipid metabolism and cell signaling; Merril, AH, Hannun, YA. Eds. 311:480-498
• Bielawska, A, Hannun, YA, Szulc, Z. (2000) Radiolabeled Sphingolipids, Part III Synthesis of Key Precursors. Methods in Enzymology: Sphingolipid metabolism and cell signaling; Merril, AH, Hannun, YA. Eds.311:518-535