Research Interests

          I am interested in the genetic and physiological mechanisms that contribute to diversity within species, i.e., intraspecific variation.  In particular, my work examines quantitative trait loci (QTL) , i.e., regions of the genome that contribute to continuous variation rather than major mutations that cause serious abnormalities.  My recent work has focused variation in growth in mice, but my current work also includes other systems such as fungi and fish, described below.  If you are interested in joining my lab, please see my information for prospective students which describes potential projects.

PAPPA2 and intraspecific variation in growth

     In my postdoctoral work, I mapped a QTL affecting growth in mice to a region containing only 4 genes, one of which is a strong candidate, PAPPA2 (Christians et al. 2006).  Two of my graduate students, Joyce Wang and Pamela Smith, are currently examining the physiological roles of this gene. 

     In particular, we are interested in the function of PAPPA2 in the placenta because of the known roles played by a related protein, PAPPA.  PAPPA is expressed at high levels in the placenta, is secreted into the maternal bloodstream and is widely used by physicians as a biomarker of placental dysfunction.

Intraspecific variation in virulence

     Aspergillus is a ubiquitous fungus that causes serious infections, particularly in immunocompromised populations such as transplant recipients.  Invasive infections are often fatal, and therefore new interventions that target the pathogen without harming the host are needed.  Natural variation in virulence within species of Aspergillus may hold clues to the nature of pathogen-specific pathways. 
     My graduate student Manjinder Cheema is currently assessing the extent of variation in virulence within Aspergillus nidulans.  This work is the first step towards mapping QTL affecting variation in virulence, and ultimately identifying new genes that contribute to the ability of this species to cause disease. 

Intraspecific variation in spinal curvature

     I am also collaborating with Felix Breden and his graduate student Kristen Gorman to map QTL influencing spinal curvature in fish as a model of human  idiopathic scoliosis.   Please click here for more detail.

Intraspecific variation in reproduction

          In the past, I have investigated the physiological mechanisms underlying variation in reproductive investment (egg size and clutch size) in birds (see more detail).  The common theme that runs throughout my research is the desire to understand the mechanistic basis of phenotypic variation.

Information for prospective students

Selected publications

Current students

Manjinder Singh Cheema (msc15@sfu.ca)
Several species within the genus Aspergillus can cause fatal infections in immunocompromised individuals including transplant recipients and patients with chronic granulomatous disease (CGD).  The overall aim of my work is to identify genes associated with virulence using quantitative trait loci (QTL) mapping.  Generally, I am interested in measuring natural variation in growth and virulence-related traits within A. nidulans, a pre-requisite for QTL mapping.  I am using Galleria mellonella larvae (wax moth) as a host model to test variation in in vivo virulence.  These findings will provide insight into variation in growth and virulence within Aspergillus species and will ultimately help to identify the genes responsible for variation using QTL mapping. 

Pamela Smith (pks9@sfu.ca)
Pregnancy-associated plasma protein A2 (PAPPA2) is a protein which has recently been shown to be differentially expressed in pre-eclampsia.  A very similar protein, PAPPA, is associated with trisomies such as Down’s syndrome, preterm delivery, low birth weight, and other adverse outcomes in humans. I am interested in the physiological role of PAPPA2 in the placenta and fetal development, as the physiological role of this protein remains unknown.  I will be using a line of conditional knockout mice, missing the PAPPA2 gene only in the placenta. I plan to observe the effects of a lack of PAPPA2 on various pregnancy outcomes such as gestational length, number of pups, and weight of pups. In continuation of the work done by Joyce Wang and her study of the wild-type expression patterns of PAPPA2, I will also study the differential histology of the placentas. A lack of PAPPA2 may also have an effect on the growth of the pups later on in life, so I will look at tail length and total mass at different intervals during their lifetimes.

Joyce Wang (jwa27@sfu.ca)
Pregnancy-associated plasma protein-A2 (PAPP-A2) cleaves insulin-like growth factor binding protein-5 (IGFBP-5), an important player in various physiological processes. Another structurally and functionally similar protease, PAPP-A, has been found to be highly upregulated during human pregnancy and is involved in the invasion of fetal placenta into maternal tissue.  Also, circulating PAPP-A levels are clinically important for diagnosing fetal disorders, such as Down’s syndrome. However, PAPP-A is not upregulated in the mouse placenta or pregnancy serum. Therefore I am interested in investigating the expression profile of PAPP-A2 in the mouse placenta during gestation to elucidate the role it plays in placental physiology and embryonic growth, as well as its potential to be used for preventive screening for pregnancy-induced complications.