DeAngelis, Paul L. PhD

Professor


Contact Information:

Office: BMSB 842A

Mailing address:
Biochemistry & Molecular Biology
940 S. L. Young Blvd., BMSB 842A
Oklahoma City, OK  73104

Phone: (405) 271-2227  ext. 61210
Fax:     (405) 271-3092

paul-deangelis@ouhsc.edu


Education:

PhD, University of California, Irvine, 1990


Research Interests:

Most life on earth, from microbes to humans, utilizes the specific interaction of proteins with carbohydrates for recognition and adhesion between cells. Our laboratory has been studying the biosynthesis of polysaccharides and oligosaccharides using the tools of biochemical analysis, carbohydrate chemistry and molecular biology.

Several projects focus on glycosaminoglycans, a class of essential polysaccharides, which includes hyaluronan, heparin and chondroitin. These molecules are found in extracellular space and/or cell surfaces throughout the human body where they play various roles in signaling, adhesion, recognition as well as structural elements. Certain pathogenic bacteria coat themselves with the identical or similar polymers to enhance infection; this molecular camouflage protects the microbe as well as potentially hijacks the host's pathways.

We are cloning and manipulating the enzymes involved in the synthesis of various glycosaminoglycan polysaccharides. We have discovered several new hyaluronan synthases, the first chondroitin synthase from any source, and two novel distinct heparosan synthases. Our overall basic science goals are to understand the fundamental mechanisms of naturally occurring enzymes. As a result of this work, we have found certain modules and motifs are responsible for specific sugar transfer reactions. This knowledge has allowed us to pursue endeavors with potential commercial applications. Some of our biotechnological research is focused on: (a) the design of novel hybrid polysaccharide molecules for medical or industrial applications, (b) the formation of biocompatible coatings and surfaces for use in sensors or other implanted devices, (c) the synthesis of defined oligosaccharides that have potential for use as anticancer agents, anticoagulants, or immune system stimulators and (d) the synthesis of sugar-based targeting drug delivery systems.


Selected Publications:

  • DeAngelis, P.L. (2015) Heparosan, a promising 'naturally good' polymeric conjugating vehicle for delivery of injectable therapeutics.  Expert Opin Drug Deliv12:349-352.

  • Lauer ME, Glant TT, Mikecz K, DeAngelis PL, haller FM, Husni ME, Hascall VC, Calabro A. Irreversible Heavy Chain Transfer to Hyaluronan Oligosaccharides by Tumor Necrosis Factor-stimulated Gene-6. J. Biol Chem. 2013 jan 4;288(1):205-214

  • Siiskonen H, Rilla K, Rilla K, Kärnä R, Bart G, Jing W, Haller MF, DeAngelis PL, Tammi RH, Tammi MI. Hyaluronan in cytosol - Microinjection-based probing of its existence and suggested functions. Glycobiology. 2013 Feb;23(2):222-231.

  • DeAngelis, P.L. (2012) Glycosaminoglycan polysaccharide biosynthesis and production: today and tomorrow. Appl. Microbiol. Biotechnology, 94:295-305.

  • Otto, N.J., Green, D.E., Masuko, S., Mayer, A., Tanner, M.E. Linhardt, R.J., and DeAngelis, P.L. (2012) Structure/function analysis of the Pasteurella multocida heparosan synthases: Towards defining enzyme specificity and engineering novel catalysts. J. Biol. Chem. 287:7203-7212.

  • Otto N.J., Solakyildirim K., Linhardt R.J., DeAngelis P.L. (2011) Comamonas testosteronan synthase, a bifunctional glycosyltransferase that produces a unique heparosan polysaccharide analog. Glycobiology21:1331-1340.

  • Weigel, P.H. and DeAngelis P.L. (2007) Hyaluronan Synthases: A Decade-plus of Novel Glycosyltransferases. J. Biol. Chem. 282: 36777-36781.

  • Sismey-Ragatz, A.E. Green, D.E., Otto, N.J., Rejzek, M. Field, RA, and DeAngelis P.L. (2007) Chemoenzymatic Synthesis with Distinct Pasteurella Heparosan Synthases; Monodisperse Polymers and Unnatural Structures J. Biol. Chem., 282:28321-28327.

  • Tracy B.S., Avci F.Y., Linhardt R.J., and DeAngelis P.L. (2007) Acceptor specificity of the Pasteurella hyaluronan and chondroitin synthases and production of chimeric glycosaminoglycans.  J. Biol. Chem. 282:337-44.

  • Kane T.A., White C.L., and DeAngelis P.L. (2006) Functional characterization of PmHS1, a Pasteurella multocida heparosan synthase. J. Biol. Chem. 281:33192-33197.

  • Jing W., Haller F.M., Almond A., and DeAngelis P.L. (2006)  Defined megaDalton hyaluronan polymer standards. Anal. Biochem. 355:183-188.

  • Williams, K.J., Halkes, K.M., Kamerling, J.P., and DeAngelis, P.L. (2006) Critical elements of oligosaccharide acceptor substrates for the Pasteurella multocida hyaluronan synthase. J. Biol. Chem. 281:5391-5397.

  • Blundell, C.D., Almond, A., Mahoney, D.J., DeAngelis, P.L., Campbell, I.D., and Day, A.J. (2005) Towards a structure for a hyaluronan-TSG-6 complex by modeling and NMR spectroscopy: Insights into other members of the link module superfamily. J. Biol. Chem. 280:18189-18201.

  • Jing, W. and DeAngelis, P.L. (2004) Synchronized Chemoenzymatic Synthesis of Monodisperse Hyaluronan Polymers. J. Biol. Chem. 279:42345-42349.

  • DeAngelis, P.L., Oatman, L.C., and Gay, D.F. (2003) Rapid Chemoenzymatic Synthesis of Monodisperse Oligosaccharides with Immobilized Enzyme Reactors. J. Biol. Chem. 278:35199-35203.

  • Jing, W. and DeAngelis, P.L. (2003) Analysis of the two active sites of the hyaluronan synthase and the chondroitin synthase of Pasteurella multocida..Glycobiology. 13:661-671.

  • Pummill, P.E. and DeAngelis, P.L. (2003) Alteration of Polysaccharide Size Distribution of a Vertebrate Hyaluronan Synthase by Mutation. J. Biol. Chem. 278:19808-19814.

  • DeAngelis, P.L. and White, C.L. (2002) Identification and molecular cloning of a heparosan synthase from Pasteurella multocida type D J. Biol. Chem. 277:7209-7213.

  • DeAngelis, P.L. and Padgett-McCue, A.J. (2000) Identification and Molecular Cloning of a Chondroitin Synthase from Pasteurella multocida Type F. J. Biol. Chem. 275:24124-24129.

  • Jing, W. and DeAngelis, P.L. (2000) Dissection of the Two Transferase Activities of the Pasteurella multocida Hyaluronan Synthase: Two Active Sites Exist in One Polypeptide. Glycobiology. 10:883-889.

  • DeAngelis, P.L. (1999) Molecular Directionality of Polysaccharide Polymerization by the Pasteurella multocida Hyaluronan Synthase. J. Biol. Chem. 274:26557-26562.

  • DeAngelis, P.L., Jing, W., Drake, R.R., and Achyuthan, A.M. (1998) Identification and Molecular Cloning of a Unique Hyaluronan Synthase from Pasteurella  multocida. J. Biol. Chem. 273:8454-8458.

  • DeAngelis, P.L., Jing, W., Graves, M.V., Burbank, D.E., and Van Etten, J.L. (1997) Hyaluronan Synthase of Chlorella Virus PBCV-1. Science.278:1800-1803

  • DeAngelis, P.L., and A.M. Achyuthan (1996) Yeast-derived DG42 Protein of Xenopus can Synthesize Hyaluronan in vitro. J. Biol. Chem. 271:23657-23660.

  • DeAngelis, P.L., Papaconstantinou, J. and Weigel, P.H.  (1993)  Molecular Cloning, Identification, and Sequence of the Hyaluronan Synthase Gene from Group A Streptococcus pyogenes.  J. Biol. Chem. 268:19181-19184

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