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Department of biochemistry and Molecular biology

Szulc Zdzislaw, PhD

Zdzislaw Szulc, Ph.D.Szulc Pic
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

Contact Info
Office: 843-792-0755
Lab: 843-792-0755
Fax: 843-792-4850


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.

Recent Publications | Additional Publications

Perera MN, Ganesan V, Siskind LJ, Szulc ZM, Bielawska A, Bittman R, Colombini M. (2016) Ceramide channel: Structural basis for selective membrane targeting. Chem Phys Lipids 194:110-16. PMID: 26408265

Bai A, Szulc ZM, Bielawski J, Pierce JS, Rembiesa B, Terzieva S, Mao C, Xu R, Wu B, Clarke CJ, Newcomb B, Liu X, Norris J, Hannun YA, Bielawska A. (2014) Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugsBioorg Med Chem 22(24):6933-44. PMID: 25456083

Kota V, Dhople VM, Fullbright G, Smythe NM, Szulc ZM, Bielawska A, Hama H. (2014) 2'-hydroxy C16-ceramide induces apoptosis-associated proteomic changes in C6 glioma cells. J Proteome Res 12(10): 4366-75. PMID: 23987666

Korbelik M, Zhang W, Saw KM, Szulc ZM, Bielawska A, Separovic D. (2013) Cationic ceramides and analogues, LCL30 and LCL85, as adjuvants to photodynamic therapy of tumors. J Photochem Photobiol B 126:72-7. PMID: 23911762.

Saddoughi SA, Gencer S, Peterson YK, Ward KE, Mukhopadhyay A, Oaks J, Bielawski J, Szulc ZM, Thomas RJ, Selvam SP, Senkal CE, Garrett-Mayer E, De Palma RM, Fedarovich D, Liu A, Habib AA, Stahelin RV, Perrotti D, Ogretmen B. (2013). Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis. EMBO Mol Med 5(1):105-21. PMID: 23180565

Beckham TH, Lu P, Jones EE, Marrison T, Lewis CS, Cheng JC, Ramshesh VK, Beeson G, Beeson CC, Drake RR, Bielawska A, Bielawski J, Szulc ZM, Ogretmen B, Norris JS, Liu X. (2013) LCL124, a cationic analog of ceramide, selectively induces pancreatic cancer cell death by accumulating in mitochondria. J Pharmacol Exp Ther 344(1):167-78. PMID: 23086228

Syed I, Szulc ZM, Ogretmen B, Kowluru A. (2012) L- threo -C6-pyridinium-ceramide bromide, a novel cationic ceramide, induces NADPH oxidase activation, mitochondrial dysfunction and loss in cell viability in INS 832/13 β-cells. Syed I, Szulc ZM, Ogretmen B, Kowluru A. Cell Physiol Biochem 30(4):1051-8. PMID: 23052231

Sentelle RD, Senkal CE, Jiang W, Ponnusamy S, Gencer S, Selvam SP, Ramshesh VK, Peterson YK, Lemasters JJ, Szulc ZM, Bielawski J, Ogretmen B. (2012)Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy. Nat Chem Biol 8(10):831-8. PMID: 22922758

Kota V, Szulc ZM, Hama H. (2012) Identification of C(6) -ceramide-interacting proteins in D6P2T Schwannoma cells. Proteomics 12(13):2179-84. PMID: 22623228

Perera MN, Lin SH, Peterson YK, Bielawska A, Szulc ZM, Bittman R, Colombini M. (2012) Bax and Bcl-xL exert their regulation on different sites of the ceramide channel. Biochem J 445(1):81-91. PMID: 22494048

Perera MN, Ganesan V, Siskind LJ, Szulc ZM, Bielawski J, Bielawska A, Bittman R, Colombini M. (2012) Ceramide channels: Influence of molecular structure on channel formation in membranes. Biochim Biophys Acta 1818(5):1291-301. PMID: 22365970

Hu X, Yang D, Zimmerman M, Liu F, Yang J, Kannan S, Burchert A, Szulc ZM, Bielawska A, Ozato K, Bhalla K, Liu K. (2011) IRF8 regulates acid ceramidase expression to mediate apoptosis and suppresses myelogeneous leukemia. Cancer Res 71(8):2882-91. PMID: 21487040

Thayyullathil F, Chathoth S, Hago A, Patel M, Szulc ZM, Hannun Y, Galadari S. (2011) 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 1811(4):242-52. PMID: 21224012

Hou Q, Jin J, Zhou H, Novgorodov SA, Bielawska A, Szulc ZM, Hannun YA, Obeid LM, Hsu YT. (2011) Mitochondrially targeted ceramides preferentially promote autophagy, retard cell growth, and induce apoptosis. J Lipid Res 52(2):278-88. PMID: 21081756

Bielawski J, Pierce JS, Snider J, Rembiesa B, Szulc ZM, Bielawska A. (2010) Sphingolipid analysis by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Adv Exp Med Biol 688:46-59. PMID: 20919645

Szulc ZM, Bai A, Bielawski J, Mayroo N, Miller DE, Gracz H, Hannun YA, Bielawska A. (2010) Synthesis, NMR characterization and divergent biological actions of 2'-hydroxy-ceramide/dihydroceramide stereoisomers in MCF7 cells. Bioorg Med Chem 18(21):7565-79. PMID: 20851613

Sun W, Jin J, Xu R, Hu W, Szulc ZM, Bielawski J, Obeid LM, Mao C. (2010) Substrate specificity, membrane topology, and activity regulation of human alkaline ceramidase 2 (ACER2). J Biol Chem 285(12):8995-9007. PMID: 20089856

Hu W, Xu R, Sun W, Szulc ZM, Bielawski J, Obeid LM, Mao C. (2010)
Alkaline ceramidase 3 (ACER3) hydrolyzes unsaturated long-chain ceramides, and its down-regulation inhibits both cell proliferation and apoptosis. J Biol Chem 285(11):7964-76. PMID: 20068046

Bielawski J, Pierce JS, Snider J, Rembiesa B, Szulc ZM, Bielawska A. (2009) Comprehensive quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography-tandem mass spectrometry. Methods Mol Biol 579:443-67. PMID: 19763489

Bai A, Szulc ZM, Bielawski J, Mayroo N, Liu X, Norris J, Hannun YA, Bielawska A. (2009) Synthesis and bioevaluation of omega-N-amino analogs of B13. Bioorg Med Chem 17(5):1840-8. PMID: 19217788

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