Education:
PhD, University of California, Irvine, 1990
Clinical/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 polysaccharide molecules for medical applications, (b) the formation of biocompatible coatings and surfaces for use in sensors or other implanted devices, (c) the synthesis of defined polymers that have potential for use as anticancer agents, anticoagulants, or immune system stimulators and (d) the synthesis of sugar-based targeting drug delivery systems.
Select Publications:
DeAngelis P.L., Zimmer J. (2023) Hyaluronan synthases; mechanisms, myths, & mysteries of three types of unique bifunctional glycosyltransferases. Glycobiology. 33(12):1117-1127. PMID: 37769351
He, P., Zhang, X., Xia, K., Green, D. E., Baytas, S., Xu, Y., Pham, T., Liu, J., Zhang, F., Almond, A., Linhardt, R. J., DeAngelis, P. L. (2022). Chemoenzymatic synthesis of sulfur-linked sugar polymers as heparanase inhibitors. Nature Communications, 13(1), 7438. PMID: 36460670.
Rivas, F., Zahid, O., Reesink., H., Peal, B., Nixon, A., DeAngelis, P.L., Skardal, A., Rahbar, E., Hall, H. (2018) Label-free analysis of physiological hyaluronan size distribution with a solid-state nanopore sensor. Nature Communications 9:1037-39.
Jing, W., Roberts, J.W., Green, D.E., Almond A., DeAngelis, P.L. (2017) Synthesis and Characterization of Heparosan-Granulocyte-Colony Stimulating Factor Conjugates: a natural sugar-based drug delivery system to treat neutropenia. Glycobiology. 27:1052-1061.
Lane, R.S., Haller, F.M., Chavaroche, A.E.S., Almond A., DeAngelis, P.L. (2017) Heparosan-Coated Liposomes for Drug Delivery. Glycobiology. 27:1062-1074.
Lane, R.S., St. Ange K., Zolghadr B., Liu X., Schäffer C., Linhardt R.J., DeAngelis P.L. (2017) Expanding glycosaminoglycan chemical space: towards the creation of sulfated analogs, novel polymers and chimeric constructs. Glycobiology. 27:646-656.
DeAngelis, P.L., Liu, J., Linhardt, R.J. (2013) Chemoenzymatic synthesis of glycosaminoglycans: Re-creating, re-modeling and re-designing nature's longest or most complex carbohydrate chains. Glycobiology. 23:764-777.
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.
Weigel, P.H. and DeAngelis P.L. (2007) Hyaluronan Synthases: A Decade-plus of Novel Glycosyltransferases. J. Biol. Chem., 282: 36777-36781.
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