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Biography

1. Research in the Ploegh lab is focused on the biochemistry of immune recognition, in the broadest sense of the word, and on aspects of cellular protein quality control. Camelid-derived antibody fragments called nanobodies play an important role in both of these areas of research. Nanobodies are small proteins (~15kDa) that retain antigen binding properties and lend themselves to a variety of chemical modifications to endow them with new functionalities. Specifically, we use nanobodies that recognize Class II MHC products, fused with autoantigens, as a means of inducing antigen-specific tolerance and treat auto-immune diseases. When used to deliver viral antigens under inflammatory conditions, such nanobody fusions serve as vaccines. Fusions of nanobodies that recognize immunoglobulin light chains with entities that recognize virus-infected cells or tumor cells, as such or in combination with cytostatic drugs, can be used as highly effective anti-viral and anti-tumor agents in vivo, with exciting prospects for clinical translation.

Cellular quality control in eukaryotes is studied in the context of the ubiquitin-proteasome system. We seek to understand how a small family (n= ~40) of E2-type ubiquitin-conjugating enzymes productively interacts with the much larger (n> ~600) family of E3-type ubiquitin ligases. We use intracellular expression of E2-specific nanobodies to manipulate interactions between particular E2s and their client E3s. In both project areas, chemical biology remains an important investigative tool.

2. Awards: Annual Prize Dutch Society of Biochemistry; Avery-Landsteiner Prize; Havinga Medal; NIH Pioneer Award (2x); Inbev-Baillet Latour Prize; member EMBO, Royal Dutch Academy of Sciences, American Academy of Arts and Sciences, National Academy of Sciences; distinguished fellow American Association of Immunologists (AAI); meritorious career award AAI; Jon van Rood Professor in chemistry of the immune system, Leiden ľ¹Ï¸£ÀûÓ°ÊÓ.

3. Senior investigator, Program in Cellular and Molecular Medicine, member of the faculty, Department of Pediatrics