One in an ongoing series of Gazette stories celebrating researchers who received support as part of a major investment by the federal government for health-care solutions and treatments on March 13.
Calcium is well known for its importance in developing strong bones.
But during pregnancy, its role becomes even more complex.
It's a subject Memorial University's Dr. Christopher Kovacs has spent a lifetime studying: How does the mineral impact the fundamental process of human development?
A recent Canadian Institutes of Health Research grant totalling $1,028,925 will enable the University Research Professor and professor of medicine, obstetrics, gynecology and biomedical science in the Faculty of Medicine to continue on his path of discovery.
"There are certain adaptations that the mother undergoes to deliver mineral to the baby during pregnancy and they differ during breastfeeding, borrowing from the mother's skeleton to provide calcium to milk," he said. "The fetus also uses different mechanisms and hormones to regulate the mineral going across the placenta and to regulate the formation of the skeleton, making it strong before birth."
Dr. Kovacs aims to uncover how these processes are regulated, how it can sometimes go awry and what can be done to intervene by using genetically engineered mouse models to look into the roles of parathyroid hormone-related protein (PTHrP).
It's a hormone that plays a critical role in maternal metabolism during pregnancy and breastfeeding and in regulating placental calcium transport and fetal skeleton development.
Dr. Chris Kovacs's research may unlock new insights into how the mother's body adapts to the intense calcium demands of pregnancy, a role that can have long-term consequences for maternal and fetal health if disrupted. Photo: RIch Blenkinsopp
"We're trying to understand the physiology, because there's a puzzle there," he said. "There are many things that maternal physiology does in pregnancy to meet the nutritional needs of the baby. In the case of calcium and bone metabolism, the pregnant mother seems to be utilizing hormones and approaches that the non-pregnant adult doesn't use.
"If we understand better how the mother does what she does, maybe there are things that we could extract from that to become treatments for calcium and bone disorders," he added.
In Dr. Kovacs' mouse models, the PTHrP gene can be turned off in specific tissues at specific times.
This allows his team to examine the impacts of the loss of the hormone.
In the first phase of his research, Dr. Kovacs will look at limiting placental production of PTHrP to see how it affects the fetus, thereby identifying the role of placental PTHrP versus PTHrP produced in the fetal skeleton and other tissues.
The second phase investigates PTHrP made in the placenta and breast tissue by the mother.
"We are hoping to eliminate the PTHrP in maternal circulation and see what happens to the mother's physiology and if there is any impact on the fetus," said Dr. Kovacs.
By clarifying these roles, the research may unlock new insights into how the mother's body adapts to the intense calcium demands of pregnancy, a role that can have long-term consequences for maternal and fetal health if disrupted.
Life-threatening condition
The third aim, and the one which potentially could take the longest, is seeking insight into a metabolic condition that affects some women called 24-hydroxylase deficiency.
The genetic disorder disrupts the body's ability to inactivate vitamin D, leading to abnormally high calcium levels, especially during pregnancy.
"If people have a pregnant or breastfeeding woman with a calcium or bone problem, they know I'm the guy to ask for advice." Dr. Chris Kovacs
Although rare, it can be life-threatening and there are few clinical guidelines for managing it.
Dr. Kovacs says the condition is poorly understood and lacks effective therapies.
"We've seen cases where mothers become very sick, and where the high calcium levels also harm the fetus. I will examine potential treatments of 24-hydroxylase deficiency using mouse models of the disease. We want to understand the underlying mechanisms and test potential therapies using our models."
Consecutive funding
The Canadian Institutes of Health Research funding puts Dr. Kovacs at 31 consecutive years of funding, from 1999 through 2030, a remarkable accomplishment for a university researcher.
He says it's "a nice record" he had no idea he would achieve when he started working at Memorial University.
"Like any researcher starting out, you think, Okay, we'll give it a shot and if it doesn't work out, I'll do entirely clinical work.' But instead, I've been able to spend 80 per cent of my time doing research and I've built up an international recognition such that if people have a pregnant or breastfeeding woman with a calcium or bone problem, they know I'm the guy to ask for advice."
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