Faculty, Graduate Program
My research focuses on the interactions between antibodies and HIV envelope glycoproteins, particularly gp41. By evaluating the capacity of specific antibodies to bind or neutralize the virus on a case-by-case basis, we can identify weaknesses in HIV in a specific and rational way. We can then design vaccine candidates that target these weaknesses and hence might elicit superior immune (antibody) responses to HIV, as mediated by their cognate B cells. We develop antibody selection strategies, and, by combining virus neutralization assays, envelope glycoprotein mutagenesis, and other biochemical approaches, we use antibodies and small molecule inhibitors to elucidate envelope protein structure-function and uncover the molecular requirements of HIV neutralization. We have identified and characterized a number of recombinant Fabs and single-chain Fvs against the HIV-1 envelope proteins, gp120 and gp41. We study neutralizing epitopes on the ectodomain of gp41 that are proximal to the membrane-spanning domain as well as those that become transiently exposed during fusion. We also immunize animals with engineered immunogens in an effort to elicit HIV neutralizing antibodies.
B.S., Molecular Biology, University of British Columbia, 1992
Ph.D., Molecular Biology, Simon Fraser University, 1999
01/02 to 12/03 - Elizabeth Glaser Pediatric AIDS Foundation Scholarship Award; 07/01 - IAS Young Investigator Award (Travel Scholarship); 01/00 to 12/01 - Natural Sciences and Engineering Research Council of Canada Post-doctoral Fellowship (NSERC PDF); 09/98 - 12/98 Graduate Fellowship (SFU) 05/96 - 05/98 NSERC Post Graduate Scholarship (PGS B) 05/94 - 05/96 NSERC PGS A 05/92 - 08/92 Faculty of Medicine Summer Student Research Scholarship (UBC)
Ingale J, Stano A, Guenaga J, Sharma SK, Nemazee D, Zwick MB & Wyatt RT (2016) High-density array of well-ordered HIV-1 spikes on synthetic liposomal nanoparticles efficiently activate B cells. Cell Rep. 15(9):1986-1999.
Leaman DP, Lee JH, Ward AB & Zwick MB (2015) Immunogenic display of purified chemically cross-linked HIV-1 spikes. J Virol. 89(13):6725-45.
Kim AS, Leaman DP & Zwick MB (2014) Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization. PLoS Pathog. 10(7):e1004271.
Gach JS, Quendler H, Tong T, Narayan KM, Du SX, Whalen RG, Binley JM, Forthal DN, Poignard P & Zwick MB (2013) A human anitbody to the CD4 binding site of gp120 capable of highly potent but sporadic cross clade neutralization of primary HIV-1. PLoS One. 8(8):e72054.