Brian Cox

Research Synopsis

Keywords: System biology, trophoblast, placenta, gene regulation, microRNA, stem cells, development, preeclampsia, pregnancy

Detailed Description:

Systems biology of development
How is a gene's expression regulated? I generate large scale data sets and apply data fusion models to identify the different regulatory mechanisms utilized during development and their dysregulation during disease. I utilize stem cell models of the early embryo to understand how cell fate decisions are made, specifically the specification and development of the trophoblast, the tissue that generated the placenta.

Systems biology of disease
The placenta is the organ that transfers nutrients and wastes between the maternal and fetal blood supply without direct mixing of the two blood systems. The placenta also maintains the physiological state of pregnancy by regulating hormone levels in the mother. The largest percentage of complications of pregnancy in humans are due to placental dysfunction, specifically intrauterine growth restriction (IUGR) and preeclampsia (PE). My other area of interest is focused on identifying the changes in gene expression that are associated with these prevalent syndromes of human pregnancy. I have used membrane proteomics to identify the proteins that are expressed specifically in the syncytial trophoblast layer that is exposed to maternal blood. This enabled the identifying different molecular subtypes of PE. In future I hope to identify proteins that are early biomarkers of different placental pathologies and generate improved mouse genetic models of these placental pathologies.

METHODS USED

Cell and Tissue Cultures: Embryonic stem cells, trophoblast stem cells

Procedures: Gene expression analysis, immunohistochemistry, mass spectrometry, microarrays, proteomics, qRT-PCR, RT-PCR, signal transduction characterization

EQUIPMENT USED

Benchtop centrifuge, culture hood, culture incubators, fluorescence microscope, gel apparatus, low O2 incubators, low- and high-speed centrifuge, low and ultralow freezers, mass spectrometer, microwave oven, plate reader, real-time/thermocycler

PRESENT TRAINEES

Ursula Nosi
Jodie Odame
Katharine Leavey
Frances Wong
David Yi Yang
Jordana Lowe

PRESENT COLLABORATIONS

Within the Department of Physiology:
John Kingdom
Peter Backx
Lee Adamson

Outside the Department of Physiology:
Thomas Kislinger, Med Biophys, UHN, Canada
Janet Rossant, Mol Gen, Sickkids, Canada
Shannon Bainbridge, University of Ottawa, Canada
William Stanford, University of Ottawa, Canada
Hitoshi Niwa, RIKEN, Japan
Minoru Ko, Keio University, Japan
Satoshi Tanaka, University of Tokyo, Japan

Appointments

Physiology