Education:
1984 BA/Biochemical Sciences Harvard
1990 PhD/Biological Sciences University of California, Irvine
Clinical/Research Interests:
Glycobiology; enzymology of carbohydrate biosynthesis; chemoenzymatic synthesis; biotechnology of drug discovery and delivery
My basic science research primarily focuses on the synthesis of polysaccharides and oligosaccharides using the tools of biochemical analysis, carbohydrate chemistry and molecular biology. We study 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. Interestingly, 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.
My contributions include the cloning and manipulating the enzymes involved in the synthesis of the glycosaminoglycan polysaccharides. We have discovered (a) the hyaluronan synthase prototypes representing three distinct classes of catalysts, (b) the first chondroitin synthase from any source, (c) the first heparosan synthases, and (d) the entirely novel testosteronan synthase (forms an isomer of heparosan). 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. We have also expanded the repertoire of sugars that can be installed into polymer chains that allow the synthesis of artificial analogs, probes, or handles at defined and desirable locations.
In addition to basic science research, this knowledge has allowed us to pursue endeavors with potential commercial applications. Some of our biotechnological research is focused on: (a) the design of customized 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 antivirals and (d) the development of sugar-based drug delivery systems for molecules and nanoparticles. As a result, our work spun out multiple inventions that created the foundation for four sugar-based biotech companies.
Funding:
Current Funding:
DeAngelis, P. L. (Principal Investigator)
"Heparanase-inhibitor technology"
Office of Technology Development Growth Fund, The University of Oklahoma
DeAngelis, P. L. (Co-Principal Investigator; Hall, A., PI, Wake Forest)
"Development of solid-state nanopore technology for improved glycosaminoglycan analytics"
NIH 2R01GM134226-05
DeAngelis, P. L. (Principal Investigator; Hannafon, B. N. Co-PI)
"Next-Generation Heparanase Inhibitors for Treatment of Endometrial Cancer"
NIH Route 66 Endometrial Cancer SPORE Developmental Research Program
Select Honors and Accomplishments:
• 2023 President’s Innovator Award, Society for Glycobiology
• 2013 Fellow, National Academy of Inventors
• 2007 Rooster Award, International Society for Hyaluronan Sciences (scientific achievement)
Select Publications:
Five 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.
Yang W, Wang L, Fang M, Sheth V, Zhang Y, Holden AM, Donahue ND, Green DE, Frickenstein AN, Mettenbrink EM, Schwemley TA, Francek ER, Haddad M, Hossen MN, Mukherjee S, Wu S, DeAngelis P.L., Wilhelm S. Nanoparticle Surface Engineering with Heparosan Polysaccharide Reduces Serum Protein Adsorption and Enhances Cellular Uptake. Nano Lett. 2022 Mar 9;22(5):2103-2111. PMID: 35166110.
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. PMID: 28973394.
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. PMID: 29044377.
Link to full publication list:
https://www.ncbi.nlm.nih.gov/pubmed?cmd=Search&term=Deangelis+PL