Dr. Isabella Caniggia

Principle Investigator, Samuel Lunenfeld Research Institute Mount Sinai Hospital, Toronto
Researcher of the month: 
Aug 2011

On a mission to improve healthy outcomes for mothers and babies

“I’ve lived two lives in my work,” says Dr. Isabella Caniggia. “One as a pediatrician; the other as a scientist. I went into pediatrics, because I had a big mission.”

Her younger sister, Alessandra, who has cerebral palsy, inspired that mission. Dr. Caniggia’s mother developed severe pre-eclampsia and diabetes before her sister’s birth. Along with a lengthy delivery, these complications led to Alessandra’s birth disorder.
Dr. Caniggia became a pediatrician in her native Italy, because she wanted to help prevent cerebral palsy in other children. She first came to Canada to pursue a PhD in pediatrics at The Hospital for Sick Children. After completing a fellowship at the University of Alabama, she returned to Toronto to study pre-eclampsia at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital. When she was awarded her first research grant, she made an important decision.

“I’ve always been fascinated by what causes disorders, particularly cerebral palsy,“ she admits. “I got so intrigued by the possibility of being able to make a difference in the scientific understanding of the genesis of pre-eclampsia that I decided to abandon the clinical side of my career and devote myself entirely to science.”

Facts about pre-eclampsia

Today, Dr. Caniggia is a leading authority on pre-eclampsia and placental development.

She and her team of researchers have made significant progress in identifying genetic biomarkers that can predict whether pregnant women will develop early or late-onset preeclampsia. The earlier that physicians detect this disease, the better the chances of healthy outcomes for mother and fetus.

“Pre-eclampsia complicates about 5% to 7% of pregnancies,” says Dr. Caniggia. “It can strike any woman, independent of social or racial background and economic status. It manifests more often in older mothers. The use of assisted reproduction has increased its incidence.”

Pregnant women with pre-eclampsia develop extremely high blood pressure and proteinuria – high levels of protein in urine as a consequence of kidney failure. These symptoms do not usually appear before women are two-thirds of the way through their pregnancies – at the beginning of the third trimester.

“Pre-eclampsia usually comes to the physician’s attention at 25 weeks of gestation,” says Dr. Caniggia. “Because it manifests so abruptly, with no warning, it can be devastating.”

The culprit behind pre-eclampsia is an abnormal placenta. Dr. Caniggia’s research has focused on the role of this organ, which nourishes the developing fetus during gestation

“We look at events that guide the fate of placental cells to understand how pre-eclampsia manifests early on and to discover the molecular basis of this pathology,” she explains.

Early detection of pre-eclampsia in sight

Dr. Caniggia and her team are working to create a useful way to detect pre-eclampsia in the first trimester of pregnancy.

A critical problem at the root of this disorder is a lack of oxygen in the placenta. Early in pregnancy, the placenta develops in a low-oxygen (hypoxic) environment, but after the first trimester, oxygen levels begin to rise dramatically.

Dr. Caniggia and her team have discovered that, if a hypoxic environment persists, levels of certain molecules – which would normally be tuned down by oxygenation – remain high in the placenta. These molecules are detrimental to placental health.

One particular molecule, HIF-1, acts as a master regulator of oxygen balance in the placenta. Dr. Caniggia and her team discovered that HIF-1 controls the expression of certain proteins, including endoglin, during this crucial period in placental development.

Dr. Caniggia believes that endoglin may serve as an early biomarker of pre-eclampsia. She has licensed this finding to two companies, who are working on developing an early detection kit for pre-eclampsia within the next 5 years. Doctors will be able to use this point-of-care kit to detect and measure high levels of endoglin in expectant mothers to assess their risk of pre-eclampsia.
“Generally, pre-eclampsia is detected when blood pressure skyrockets at about 25 weeks of gestation,” she says. “This kit could make a real difference by detecting pre-eclampsia in about half that time – as early as 10 or 12 weeks of gestation. It would be a major asset to the clinical community.”

Mission moves forward

Dr. Caniggia’s mission to improve the health of mothers and newborns forges ahead. Her current work focuses on how to differentiate pre-eclampsia from other disorders that harm the mother and fetus, such as intrauterine growth retardation (IUGR), which leads to abnormally small birth weight, and HELLP syndrome, which may cause maternal and infant death.

They are trying to identify the molecular signatures of these disorders. This work will help doctors to detect these problems earlier and treat them during pregnancy to improve the health of newborns and mothers.   
“If we begin to understand the genesis of these diseases, if we can detect women at risk early on in pregnancy, then we can start to develop therapies,” Dr. Caniggia explains.  

For further information, please contact Dr. Isabella Caniggia using the Email contact form