Department of biochemistry and Molecular biology
Szulc Zdzislaw, PhD
Zdzislaw Szulc, Ph.D.
Research Associate Professor
Biochemistry and Molecular Biology
1997 Research Associate, Duke University Medical Center, Durham, NC
1989 Postdoctoral Chemist, Research Triangle Institute, RTP, NC
1987 Postdoctoral Fellow, Department of Chemistry, Princeton University, Princeton, NJ
1979 Ph.D., Technical University of Wroclaw, Wroclaw, Poland
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.
Recent Publications | Additional Publications
1. Kota V, Szulc ZM, Hama H. Identification of C(6) -ceramide-interacting proteins in D6P2T Schwannoma cells. Proteomics 2012; 12(13):2179-84. PMID: 22623228
2. Perera MN, Lin SH, Peterson YK, Bielawska A, Szulc ZM, Bittman R, Colombini M. Bax and Bcl-xL exert their regulation on different sites of the ceramide channel. Biochem J 2012; 445(1):81-91. PMID: 22494048
3. Perera MN, Ganesan V, Siskind LJ, Szulc ZM, Bielawski J, Bielawska A, Bittman R, Colombini M. Ceramide channels: Influence of molecular structure on channel formation in membranes. Biochim Biophys Acta 2012; 1818(5):1291-301. PMID: 22365970
4. Hu X, Yang D, Zimmerman M, Liu F, Yang J, Kannan S, Burchert A, Szulc ZM, Bielawska A, Ozato K, Bhalla K, Liu K. IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia. Cancer Res 2011; 71(8):2882-91. PMID: 21487040
5. Thayyullathil F, Chathoth S, Hago A, Patel M, Szulc ZM, Hannun Y, Galadari S. Purification and characterization of a second type of neutral ceramidase from rat brain: a second more hydrophobic form of rat brain ceramidase. Biochim Biophys Acta 2011; 1811(4):242-52. PMID: 21224012
6. Hou Q, Jin J, Zhou H, Novgorodov SA, Bielawska A, Szulc ZM, Hannun YA, Obeid LM, Hsu YT. Mitochondrially targeted ceramides preferentially promote autophagy, retard cell growth, and induce apoptosis. J Lipid Res 2011; 52(2):278-88. PMID: 21081756
7. Bielawski J, Pierce JS, Snider J, Rembiesa B, Szulc ZM, Bielawska A. Sphingolipid analysis by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Adv Exp Med Biol 2010; 688:46-59. PMID: 20919645
8. Szulc ZM, Bai A, Bielawski J, Mayroo N, Miller DE, Gracz H, Hannun YA, Bielawska A. Synthesis, NMR characterization and divergent biological actions of 2'-hydroxy-ceramide/dihydroceramide stereoisomers in MCF7 cells. Bioorg Med Chem 2010; 18(21):7565-79. PMID: 20851613
9. Sun W, Jin J, Xu R, Hu W, Szulc ZM, Bielawski J, Obeid LM, Mao C. Substrate specificity, membrane topology, and activity regulation of human alkaline ceramidase 2 (ACER2). J Biol Chem 2010 Mar 19; 285(12):8995-9007. Epub 2010 Jan 20. PubMed PMID: 20089856; PubMed Central PMCID: PMC2838321
10. Hu W, Xu R, Sun W, Szulc ZM, Bielawski J, Obeid LM, Mao C. Alkaline ceramidase 3 (ACER3) hydrolyzes unsaturated long-chain ceramides, and its down-regulation inhibits both cell proliferation and apoptosis. J Biol Chem 2010 Mar 12; 285(11):7964-76. Epub 2010 Jan 12. PubMed PMID: 20068046; PubMed Central PMCID: PMC2832947
11. Bielawski J, Pierce JS, Snider J, Rembiesa B, Szulc ZM, Bielawska A. Comprehensive quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry. Methods Mol Biol 2009; 579:443-67. PubMed PMID: 19763489
12. Bai A, Szulc ZM, Bielawski J, Mayroo N, Liu X, Norris J, Hannun YA, Bielawska A. Synthesis and bioevaluation of omega-N-amino analogs of B13. Bioorg Med Chem 2009 Mar 1;17(5):1840-8. Epub 2009 Jan 31. PubMed PMID: 19217788; PubMed Central PMCID: PMC2696190