Department of biochemistry and Molecular biology
Jacek Bielawski, PhD
Biochemistry and Molecular Biology
1996-2001 Senior Scientist, Glaxo-Wellcome, Research Triangle Park, NC
1993-1996 R&D Senior Chemist, Southern Testing and Research Labs, Wilson, NC
1989-1993 Quality Assurance, Triangle Labs, Research Triangle Park, NC
1987-1989 Environmental Chemist, NC Dept of Health and Natural Resources
1985-1987 Research Associate, University of California at Berkeley
1984-1985 Research Associate, University of Kentucky at Lexington, Lexington, KY
1977-1984 Assistant Professor, Technical University of Wroclaw, Wroclaw, Poland
1975-1977 Research Technical Associate, Technical University of Wroclaw, Wroclaw, Poland
1975 Ph.D., Technical University of Wroclaw, Wroclaw, Poland
1969 M.S., Technical University of Wroclaw, Wroclaw, Poland
During the academic tenure, my research has focused on synthetic and analytical chemistry of pesticides. New synthetic methods for the preparation of heterocyclic compounds with oxygen, sulfur, nitrogen and boron have been developed. A large number of new pesticides, as well as their radiolabeled analogues, have been synthesized to investigate structure/activity relationship, metabolism and mode of action. My research has also included extensive work in analytical chemistry of pesticides, data interpretation and structure determination using GC, GC/MS, HRGC/HRMS, HPLC, LC/MS, TLC, FAA, GFAA, ICP, multinuclear NMR, IR, and UV/VIS techniques. Most recently, I have performed analysis of new drugs and their metabolites in biological tissues by HPLC, LC/MS and RIA, and have provided analytical support of new drugs for Brain Blood Barrier, Gastrointestinal Absorption and Pharmacokinetic studies. Studies have involved development and validation of the protocols for analysis of a large number of experimental drugs from "in vitro" and "in vivo" experiments by HPLC, LC/MS, LC/MS-MS and RIA methods. I have also developed and validated generic screens for plasma protein binding and in "in vitro" metabolic stability. My work has also involved development of new, or improvement of existing, analytical methods for determination of trace residues of pesticides and drugs, their intermediates and metabolites as well as priority polluntants in a variety of matrices. In my future research, I will concentrate on the role of sphingolipids in signal transduction and cell regulation in cancer biology. Sphingolipid metabolism assumes a key role in the complex mechanisms regulating cellular stress responses to environmental inducers. Several sphingolipid metabolites have recently been shown to have bioactivity, and their individual contributions to the regulatory pathways that govern cell growth are currently being established. The Sphingomyelin (SM) cycle, a ubiquitous signaling system linking a specific set of cell-surface receptors to the nucleus and cellular events, represents a novel antiproliferative signal transduction pathway that regulates cell cycle arrest, differentiation, and apoptosis. Ceramide, the putative second messenger of the SM cycle, has been proposed as a molecular sensor of injury and assumes a fundamental role in the cellular stress response. This discovery has created the need to examine changes in sphingolipid metabolism and composition (especially ceramide), and offers promises for new molecular insights into tumor growth and metastasis. Using my strong background in synthetic and analytical chemistry, I will focus on establishing a state-of-the-art analytical facility to support this research. My goal is to develop insight into the mechanism of action of sphingolipids through the data generated by well established analytical foundation. Development of new, mostly LC/MS analytical protocols, will provide medical investigators with the powerful tools to monitor changes in sphingolipid/lipid composition in normal and cancer environments and will provide one of the missing linkages in the search for effective therapy.
Recent Publications | Additional Publications
Devillard R, Galvani S, Thiers JC, Guenet JL, Hannun Y, Bielawski J, Nègre-Salvayre A, Salvayre R, Augé N. Stress-induced sphingolipid signaling: role of type-2 neutral sphingomyelinase in murine cell apoptosis and proliferation. PLoS One. 2010 Mar 23;5(3):e9826. PubMed PMID: 20352118; PubMed Central PMCID:PMC2843740.
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.
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.
Separovic D, Kelekar A, Nayak AK, Tarca AL, Hanada K, Pierce JS, Bielawski J.Increased ceramide accumulation correlates with downregulation of the autophagy protein ATG-7 in MCF-7 cells sensitized to photodamage. Arch Biochem Biophys. 2010 Feb 1;494(1):101-5. Epub 2009 Nov 26. PubMed PMID: 19944062; PubMed Central PMCID: PMC2877393.
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.
Senkal CE, Ponnusamy S, Bielawski J, Hannun YA, Ogretmen B.Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways. FASEB J. 2010 Jan;24(1):296-308. Epub 2009 Sep 1. PubMed PMID: 19723703; PubMed Central PMCID: PMC2797032.