The
work of Michael Rieder is directed to understanding how adverse
drug reactions develop, how to predict the risk for adverse drug
reactions and how to design safer and more effective drugs. His
particular focus is on adverse drug reactions mediated by reactive
drug metabolites. Many commonly used and important drugs are metabolized,
at least in part, to reactive intermediates. Under certain circumstances,
such as in the setting of HIV infection, this may substantially
increase the risk of developing adverse drug reactions. These
metabolites can act directly on cells, inhibiting key cellular
functions, and may also generate undesirable immune responses
or inhibit protective immune responses. Dr. Rieder is investigating
these mechanisms along several lines of research, including studying
how HIV infection alters cellular responses to reactive drug metabolites.
Dr. Rieder's laboratory has recently demonstrated that specific
HIV proteins appear to change the ability of cells to interact
with reactive drug metabolites, markedly increasing the sensitivity
of these cells to reactive drug metabolites and increasing the
risk of adverse drug reactions in the setting of HIV infection.
Dr. Rieder has established that reactive metabolites of certain
drugs have profound effects on T-cell activation, and is currently
studying where these effects occur at the molecular level, focusing
on Jak-Stat kinases, which are key intracellular components that
signal lymphocyte activation. In order to better understand how
delayed-type hypersensitivity occurs, Dr. Rieder is developing
an animal model of drug hypersensitivity that can be used to pursue
in vivo observations which have been made in vitro.
Key Research Issues:
Defining the relationship between viral infection, notably HIV
infection, altered cellular metabolism and immune responses, and
adverse drug reactions.
Understanding how cellular signaling pathways are effected by
reactive drug metabolites. Determining how immune responses are
altered in the presence of reactive drug metabolites and how this
is manifested as delayed-type hypersensitivity.
EDUCATION
& AWARDS:
Education M.D., University
of Saskatchewan, Saskatoon, Saskatchewan
Ph.D., University of Toronto, Toronto, Ontario
Training Wayne State University, Detroit, Michigan
University of Toronto, Toronto, Ontairo
Awards Operating Grant, Canadian Institutes of Health Research
Opportunity Grant, Canadian Institutes of Health Research
Operating Grant, Ontario HIV Treatment Network
Operating Grant, Genome Canada
Leon Goldberg Young Investigators Award, American Society of Clinical
Pharmacology & Therapeutics
K.F. Piafsky Young Investigators Award, Canadian Society for Clinical
Pharmacology
SELECTED
PUBLICATIONS:
1. Almawi WY, Assi JW, Chudzik DM, Abou Jaoude MM, Rieder MJ:
Inhibition of cytokine production and cytokine-stimulated T-cell
activation
by FK506 (Tacrolimus) 1. Cell Transplantation (2001) 10, 615-623.
2. Manchanda T, Hess D, Dale L, Ferguson SG, Rieder MJ: Haptenation
of sulfonamide reactive metabolites to cellular proteins. Mol
Pharmacol
(2002) 62:1011-1026.
3 . Ralph ED, John M, Rieder MJ, Bombassaro AM: Serum sickness-like
reaction possibly associated with meropenem use. J Clin Inf Diseases
(2003) 36#10 (May 15):149-151.
CONTACT INFO
Michael J. Rieder
Bio Therapeutics Research Group
Robarts Research Institute
P.O. Box 5015, 100 Perth Drive
London, ON N6A 5K8
Canada
Phone: (519) 931-5777 ext. 24209 Fax: (519) 931-5789
E-mail: mrieder@uwo.ca
Paula Huegin
Secretary to Dr. Michael Rieder
Department of Paediatrics
Children's Hospital of Western Ontario
800 Commissioners
Road East
London, ON N6C 2V5
email: paula.huegin@lhsc.on.ca
telephone: (519) 685-8293
fax: (519) 685-8156
Ilda Moniz
Administrative Assistant
imoniz@robarts.ca
(519) 931-5718
