MMI Faculty
Larry Guilbert, PhD
Dept. of Medical Microbiology & Immunology
University of Alberta
Faculty of Medicine & Dentistry
6-25E Heritage Medical Research Centre
T6G 2S2 Edmonton, AB
Canada
Ph : (780) 492-4910
Fx : (780) 492-9828
Em: larry.guilbert@ualberta.ca
Positions:
- Professor, Dept. of Medical Microbiology & Immunology
Research:
Fewer than 20 infectious pathogens transmit in utero to the fetus and less than half of fetuses at risk are born infected indicating a very effective maternal-fetal immune barrier that sometimes fails. Research in my laboratory deals with the mechanisms of failure leading to in utero transmission of HIV-1, CMV, and toxoplasma. There are maternal, and probably fetal, immune defenses to maternal infections, as well as a physical barrier, the trophoblast, an epithelial cell layer that separates all fetal from maternal tissue. All three levels of defenses are being studied.
We propose that leukocyte-borne pathogens cross the syncytiotrophoblast, which faces maternal blood in the villous placenta, by either infecting or damaging it. This hypothesis is examined by studying by leukocyte adhesion to the syncytiotrophoblast, its infection by either free or cell-borne pathogens and its damage by activated leukocyte. The studies are carried out on cultured syncytiotrophoblast that is 99.99% pure and mechanisms predicted in culture are verified by examination of placental tissue from women with AIDS, CMV, or toxoplasmosis.
In utero disease transmission cannot be studied without a basic understanding of maternal immunity and placental function. We therefore also ask whether pregnancy alters immune cytokine balances and maternal immune defences against infectious disease, and whether these same cytokines affect trophoblast development and function.
People:
- Bonnie Winkler-Lowen (Technologist)
- Meghan Riddell (Graduate Student - co-supervised)
Publications:
Selected Publications:
- Guilbert LJ, Winkler-Lowen B, Sherburne R, Rote NS, Li H, Morrish DW. Preparation and functional characterization of villous cytotrophoblasts free of syncytial fragments. Placenta 23:175-83 2002
- Hemmings DG, Guilbert LJ. Polarized release of human cytomegalovirus from placental trophoblasts. J Virol 76:6710-7 2002
- Chan G, Hemmings DG, Yurochko AD, Guilbert LJ. Human Cytomegalovirus-Caused Damage to Placental Trophoblasts Mediated by Immediate-Early Gene-Induced Tumor Necrosis Factor-alpha. Am J Pathol 161:1371-81. 2002
- Mackova M, Kilani RT, Davidge ST, Guilbert LJ. The effect of oxygen tension on intracellular survival signalling in primary villous trophoblasts. Placenta. 24:627-37. 2003
- Abbasi M, Kowalewska-Grochowska K, Bahar MA, Kilani RT, Winkler-Lowen B, Guilbert LJ. Infection of Placental Trophoblasts by Toxoplasma gondii. J Infect Dis. 188:608-16. 2003
