Glenn D. Prestwich
Presidential Professor of Medicinal Chemistry and Research Professor of Biochemistry
B.S. California Institute of Technology
Ph.D. Stanford University
Research
The research in my laboratories includes organic synthesis, enzymology, molecular cloning and protein expression, cell biology, biomaterials preparation and analysis, and analysis of ligand binding.
1. Chemical Cell Biology: Visualizing Phosphoinositide (PtdInsPn) and Phospholipid (PL) Signaling in Cells. Tetherable analogs of all inositol polyphosphates (InsPns) and phosphatidylinositol polyphosphates (PtdInsPns) have been made to characterize PtdInsPn signaling proteins. Recently, derivatives of phosphatidic acid (PA), phosphatidylcholine (PC) and lysophosphatidic acid (LPA) and lysophosphatidylserine (lyso-PS) have been synthesized to study proteins important in endo- and exocytosis, signal transduction and cytoskeletal remodeling in dozens of collaborative projects. Fluorogenic substrates for phospholipases permit study of intracellular enzymology. New cell-permeant systems using fluorescent PtdInsPns and PLs show localization, movement, and metabolism in living cells. Specific antibodies to PtdInsPns and PLs and immobilized PtdInsPns allow study of how these signaling lipids are modified during alterations in cell physiology. Metabolically-stabilized analogs of LPA are synthesized and evaluated for selective activation of the nuclear PPARg and membrane-bound G-protein coupled edg (LPA) receptors.
2. Glycosaminoglycan Biomaterials for Wound-Healing, Drug Delivery and Tissue Engineering. Both hyaluronan (HA) and chondroitin sulfate (CS) can be covalently modified to produce novel hydrogel biomaterials. Specific medical applications include: (i) hydrogels for 3D tumor cell culture; (ii) in situ crosslinkable mimetics of the extracellular matrix (ECM) for tissue engineering and wound-healing; (iii) sustained local release of growth factors; (iv) more effective HA materials for preventing post-surgical adhesions; and (v) tumor-targeted anti-cancer drugs. Research is directed at materials for treatment of human vocal insufficiency, treating burn patients, sinus surgery, repair of eardrums, cartilage repair, reconstructive plastic surgery, vascular grafts, and creating new synthetic analogs of the ECM.
Cleavage of Fluorogenic Phospholipids in Mixed Micelles by Bee Venom Phospholipase A2
References
1. Zhang H, Xu Y, Zhang Z, Liman ER, Prestwich GD (2006) Synthesis and Biological Activity of Phospholipase C-Resistant Analogues of Phosphatidylinositol 4,5-bisphosphate. J. Am. Chem. Soc. 128:5642-5643
2. Ferguson CG, Bigman CS, Richardson RD, van Meeteren LA, Moolenaar WH, Prestwich GD (2006) Fluorogenic Phospholipid Substrate to Detect Lysophospholipase D/Autotaxin Activity. Organic Lett. 8:2023-2026
3. Pike DB, Cai S, Pomraning KR, Firpo MA, Fisher RJ, Shu XZ, Prestwich GD, Peattie RA (2006) Heparin-regulated Release of Growth Factors In Vitro and Angiogenic Response In Vivo to Implanted Hyaluronan Hydrogels Containing VEGF and bFGF. Biomaterials 27:5242-5251
4. Rose TM, Prestwich GD (2006) Synthesis and Evaluation of Fluorogenic Substrates for Phospholipase D and Phospholipase C. Organic Lett. 8:2575-2578
5. Rose TM, Prestwich GD (2006) Fluorogenic Phospholipids as Head Group-Selective Reporters of Phospholipase A Activity. ACS Chemical Biology 1:63-92
6. Xu Y, Lee SA, Kutateladze TG, Sbrissa D, Shisheva A, Prestwich GD (2006) Chemical Synthesis and Molecular Recognition of Phosphatase-Resistant Analogues of Phosphatidylinositol-3-phosphate. J. Am. Chem. Soc. 128:885-897
7. Liu Y, Ahmad S, Shu XZ, Sanders RK, Kopesec SA, Prestwich GD (2006) Accelerated Repair of Cortical Bone Defects Using a Synthetic Extracellular Matrix to Deliver Human Demineralized Bone Matrix. J. Orthoped. Res. 24:1454-1462
8. Ghosh K, Ren X-D, Shu XZ, Prestwich GD, Clark RAF (2006) Fibronectin Functional Domains Coupled to Hyaluronan Stimulate Adult Human Dermal Fibroblast Responses Critical for Wound Healing. Tissue Eng. 12:601-613
9. Liu Y, Ahmad S, Shu XZ, Sanders RK, Kopesec SA, Prestwich GD (2006) Accelerated Repair of Cortical Bone Defects Using a Synthetic Extracellular Matrix to Deliver Human Demineralized Bone Matrix. J. Orthoped. Res. 24:000-000
10. Peattie RA, Rieke E, Hewett E, Fisher RJ, Shu XZ, Prestwich GD (2006) Dual Growth Factor-Induced Angiogenesis In Vivo Using Hyaluronan Hydrogel Implants. Biomaterials 27:1868-1875
11. Ferguson CG, James RD, Bigman CS, Shepard DA, Abdiche Y, Katsamba PS, Myszka DG, Prestwich GD (2005) Phosphoinositide-Containing Polymerized Liposomes: Stable Membrane-Mimetic Vesicles for Protein-Lipid Binding Analysis. Bioconjugate Chem. 16:1475-1483
12. Ghosh K, Ren XD, Shu XZ, Prestwich GD, Clark RAF (2006) Fibronectin Functional Domains Coupled to Hyaluronan Stimulate Adult Human Dermal Fibroblast Responses Critical for Wound Healing. Tissue Eng. 12:601-613
13. Mironov V, Kasyanov V, Shu XZ, Eisenberg C, Eisenberg L, Gonda S, Trusk T, Markwald RR, Prestwich GD (2005) Fabrication of Tubular Tissue Constructs by Centrifugal Casting of Cells Suspended in an In Situ Crosslinkable Hyaluronan-Gelatin Hydrogel. Biomaterials 26:7628-7635
14. Cai S, Liu Y, Shu XZ, Prestwich GD (2005) Injectable Glycosaminoglycan Hydrogels for Controlled Release of Basic Fibroblast Growth Factor. Biomaterials 26:6054-6067
15. Xu Y, Aoki J, Shimizu K, Umezu-Goto M, Hama K, Takanezawa T, Yu S, Mills GB, Arai H, Qian L, Prestwich GD (2005) Structure-activity Relationships of Fluorinated Lysophosphatidic Acid Analogues. J. Med. Chem. 48:3319-3327
16. Liu Y, Li H, Shu XZ, Gray SD, Prestwich GD (2005) Crosslinked Hyaluronan Hydrogels Containing Mitomycin C Reduce Post-operative Abdominal Adhesions. Fertil. & Steril. 83:1275-1283
17. Li H, Liu Y, Shu XZ, Gray SD, Prestwich GD (2004) Synthesis and Biological Evaluation of a Cross-Linked Hyaluronan-Mitomycin C Hydrogel. Biomacromolecules 5:895-902
18. Prestwich GD (2004) Phosphoinositide Signaling: From Affinity Probes to Pharmaceutical Targets. Chem. & Biol. 11:619-637
