Christopher E. Rudd

Christopher Edward Rudd is a Canadian-born immunologist-biochemist. He is currently Professor of Medicine at the Universite de Montreal and Director, Immunology-Cell Therapy at the Centre de Recherche Hôpital Maisonneuve-Rosemont.

Early life and education

Chris Rudd was born in Toronto, Ontario, Canada on November 2, 1963. He was educated at the Jesuit-run Brebeuf College School and at McGill University in Montreal, received an MSc degree from the Universite d'Ottawa, PhD and DSc degrees from University College, London and an MA from the University of Cambridge. He has held professorship positions at Harvard Medical School and Imperial College London and was Professor of Molecular Immunology at the University of Cambridge.^[1].

Research

Rudd is credited with having had a major impact on the understanding of the intracellular signals that control T-cell immunity. Rudd was the first^[1] to discover that intracellular protein kinases interact with surface receptors, by identifying the interaction of T-cell co-receptors CD4 (also the receptor for the human immunodeficiency virus, HIV-1) and CD8 on T-cells with protein-tyrosine kinase p56lck. His discovery provided a role for members of the proto-oncogene pp60src kinase family in normal cell signaling. Other receptors were later found to use src-related kinases to regulate cell growth. In terms of immunology, the CD4- and CD8-p56lck complexes are now widely accepted as the initiators of the T cell activation, leading to the recruitment of a second tyrosine kinase ZAP-70 that control the ability of T-cells to respond to foreign pathogens, foreign transplants and cancer cells.

Rudd has also elucidated the signaling mechanisms by which co-receptors CD28, CTLA-4 and ICOS1 modulate T-cell responses. By showing that CTLA-4 activates T-cell motility and migration, he has proposed the 'reverse-stop signal model' to account for CTLA-4 down-regulation of conventional T-cell responses to antigen. His research has also shown that a mutant form of an immune adapter protein termed ADAP can block the infection of T-cells by the Human Immunodeficiency Virus (HIV-1), and has pioneered the use of small molecule inhibitors (SMIs) of glycogen synthase kinase-3 (GSK-3) in the down-regulation of the co-receptor programmed cell death-1 (PD-1) in immunotherapy.

Rudd's work has had important clinical outcomes as it laid the foundation for chimeric antigen receptor (CAR) cancer therapy that has been pioneered by Zelig Eshhar (Israel) and Carl June (USA). T cells transduced with chimeric receptors to recognize and kill cancer cells have employed immunoreceptor tyrosine-based activation motifs (ITAMs) (a target of p56lck), as well as CD28 signaling motifs that were identified by Rudd's lab.

Recognition

Rudd has received awards including the Cancer Research Institute/Benjamin Jacobson Family Investigator Award (New York), Claudia Adams Barr Research Award (Boston) and was a Scholar of the Leukemia Society of America and a Principal Research Fellow (PRF) of the Wellcome Trust. He was elected a Fellow of the Royal College of Pathologists (FRCPath) and the Academy of Medical Sciences (FMedSci). Over the years Rudd has trained many graduate students at Ph.D. level, some of whom hold prestigious academic positions in different parts of the world.

His nomination as a Fellow of the Academy of Medical Sciences (FMedSci) in 2002 reads:^[2]

He has made major contributions to our understanding of T cell activation, and has defined several of the key molecular pathways that connect cell membrane receptor ligation with gene transcription. In particular he made the seminal discovery that that CD4 and CD8 co-receptor molecules are linked to the p56 lck src family kinase. These complexes are now widely accepted as the initiators of T cell activation of phosphorylation of several key substrates. These observations have had important implications in the field of oncology, since for the first time, a function was provided for the p60 src family of proto-oncogenes in normal cell growth.

Publications

• Rudd CE, Trevillyan JM, Wong LL, Dasgupta JD, Schlossman SF. (1998) The CD4 receptor is complexed to a T-cell specific tyrosine kinase (pp58) in detergent lysates from human T lymphocytes. Proc Nat'l Acad Sci USA. 85, 5190-94.
• Barber, EK, Dasgutpa JD, Schlossman SF, Trevillyan JM, Rudd CE. (1989) The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex. Proc. Nat'l. Acad. Sci. USA 86, 3277-81.
• Rudd CE. CD4, CD8 and the TcR/CD3 Complex: a novel class of protein tyrosine kinase receptor (1990) Immunology Today, 11, 400-406
• Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, Wei B, Hogg N, G Garside P, Rudd CE. (2006) Reversal of the TCR stop signal by CTLA-4. Science. 313,1972-5.
• Wei B, Han L, Abbink TEM, Elisabetta G, Lim D, Thaker R, Gao W, Wang J, Lever A, Jolly C, Wang H, Rudd CE (2013) Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors. Retrovirol. 10 (1):101.

References