M. Edward Medof, MD, PhD

Previous research in the lab has included:

1. Elucidation of the function of immune adherence receptors (CR1) on red blood cells and original description of the red cell immune complex clearance system.
2. Discovery that CR1 plays an essential role in the generation of C3dg, the C3 fragment that activates B cells.
3. Initial proposal of the concept that two sets of cell-associated complement regulators, i.e. intrinsic and extrinsic, exist.
4. Discovery, purification and characterization of DAF or CD59, the regulator which distinguishes self from non-self.
5. Characterization of DAF's function in disabling autologous C3 and C5 convertases on self cell surfaces.
6. Original preparation of anti-DAF mAbs and analyses of the tissue distribution of surface and soluble DAF proteins in body fluids.
7. Clarification of how DAF and MCP cooperate in controlling self cell associated C3/C5 convertases.
8. Cloning of DAF cDNA.
9. Documentation of the relationship of DAF and CD59 deficiency to the complement sensitivity in the hemolytic disorder, paroxysmal nocturnal hemoglobinuria (PNH).
10. Demonstration that DAF is attached to cell membranes by a glycosylphosphatidylinositol (GPI)-anchor.
11. Determination that the biochemical defect in affected PNH cells resides in GPI anchor synthesis.
12. Characterization of the mammalian intracellular GPI-anchor assembly pathway in the ER.
13. Cloning of the GPI transamidase that provides for GPI transfer to proproteins.
14. Localization of the biochemical/genetic step that underlies defective GPI synthesis in PNH.
15. Characterization of genetic alterations in affected cells of different PNH patients.
16. Characterization of the signals in nascent proproteins which direct GPI attachment.
17. Initial description and development of the technique of protein engineering or "painting" of cells with GPI reanchored proteins as an alternative to gene transfer for multiple purposes including the production of tumor cell vaccines.
18. Preparation of DAF knockout and PNH knockout mice.
19. Clarification of the mechanism of acetylcholine receptor loss in myasthenia gravis.
20. NMR 3D structural characterization of DAF.
21. Mapping of DAF's active site(s) by substitution mutagenesis.
22. Discovery of the role of local complement synthesis of antigen presenting cell, T-cell partners in T-cell costimulations.
23. Discovery of the role of C3a and C5a receptors in cell viability and cell growth.