Affiliate Investigator, Child and Family Research Institute
I am interested in the genetic and physiological mechanisms that contribute to diversity within species, i.e., intraspecific variation. Much of my recent work has examined quantitative trait loci (QTL), i.e., regions of the genome that contribute to continuous variation rather than major mutations that cause serious abnormalities. While I have focused primarily on growth in mice, I also work with humans, fish and fungi. Prior to moving into the field of genetics, I studied ecological physiology and variation in reproductive effort in birds. If you are interested in joining my lab, please see my information for prospective students which describes potential projects.
My previous work identified pregnancy-associated plasma protein A2 (PAPP-A2) as the gene responsible for a QTL affecting body size in mice (Christians et al. 2006, Christians et al. 2013). Little is known about the physiological roles of PAPP-A2, and my current work focuses on the roles of this protein in skeletal and placental development.
Role of PAPP-A2 in skeletal development
PAPP-A2 is a protease of insulin-like growth factor
binding protein 5 (IGFBP-5), and IGFBP-5 is known to
play a role in bone metabolism. Furthermore, the
QTL described above affects bone lengths in mice, as
does knocking out the PAPP-A2 gene. Questions we
are currently studying include:
- Are the effects of PAPP-A2 on postnatal growth due primarily to its actions in bone?
- Does PAPP-A2 influence bone shape as well as size, and could this affect predisposition to conditions such as hip dysplasia?
Role of PAPP-A and PAPP-A2 in placental development
The placenta is responsible for the transfer of
nutrients and oxygen from a pregnant woman to her
fetus. The proper development, growth, and
function of the placenta is therefore critical for
healthy fetal development. Abnormal placentation
threatens the health of both the fetus and of the
mother, potentially causing conditions such as
preeclampsia, a leading cause of maternal morbidity
and mortality. Although preeclampsia affects
5-7% of pregnancies, it remains
Recently, a number of studies have identified associations between the placental levels of PAPP-A2 and preeclampsia. Furthermore, numerous studies have found associations between the levels of PAPP-A, a protein structurally and functionally similar to PAPP-A2, and a number of different complications of pregnancy, including low birth weight, preterm delivery, pregnancy loss, and preeclampsia. However, it is not clear whether altered levels of PAPP-A and PAPP-A2 cause abnormal placental development, or whether the production of these proteins is altered to compensate for abnormal placentation (Christians and Gruslin 2010). We have started to address this issue using mice (Wang et al. 2009, Wagner and Christians 2010), cell culture (Wagner et al. 2011) and tissue culture. Recently, we also obtained a Nelly Auersperg Award from the Women's Health Research Institute of BC to examine whether first trimester PAPP-A2 levels are associated with adverse pregnancy outcomes.