Alexandre Orthwein
Assistant Professor
Microbiology & Immunology
McGill University
Canada
Biography
Lady Davis Institute, Jewish General Hospital
Research Interest
Genetic diversity is crucial for B-cells to generate a large repertoire of antibodies capable of recognizing and eliminating the infinite spectrum of pathogens. This process relies mainly on the generation of cytotoxic DNA lesions, in particular DNA double-strand breaks (DSBs), which are predominantly targeted to the Immunoglobulin/antibody genes during B-cell development. Successful DSB repair results in antibody diversification and the establishment of a functional immune response. Inversely, improper repair can result in immunodeficiency syndromes characterized by recurrent infections. Approximately 29,000 Canadians suffer from primary immunodeficiency syndromes and about 70% of them are undiagnosed. Off-targets DSBs can also lead to chromosomal translocations, which fuel B-cell malignancies, including lymphoma, leukemia and multiple myeloma. These hematological malignancies represent the fourth most common type of cancer in Canada and despite considerable therapeutic advances most of the patients affected by aggressive hematological cancer are incurable.
Publications
-
Montamat-Sicotte D, Safavi S, Abreu C, Litzler LC, Zahn A, Orthwein A, Muschen M, Oppezzo P, Munoz DP, Di Noia JM. HSP90 inhibitors decrease AID levels and activity in mice and human cells. Eur J Immunol. 45(8) :2365-76.
-
Orthwein A*, Noordermeer S*, Wilson MD, Landry S, Enchev RI, Sherker A, Munro M, Pinder J, Salsman J, Dellaire G, Xia B, Peter M, Durocher D. A mechanism for suppression of homologous recombination in G1 cells. Nature. 528(7582):422-6 (* co-first authors)
-
Tkac J*, Xu G*, Adhikary H, Young JTF, Gallo D, Escribano-Diaz C, Krietsch J, Orthwein A, Munro M, Sol W, Al-Hakim A, Lin ZY, Jonkers J, Piet B, Brown GW, Gingras AC, Rottenberg S, Masson JY, Durocher D. HELB is a feedback inhibitor of DNA end resection. Mol Cell (2016) 61(3):405-18 (* co-first authors)
