After hearing leading nephrologist, clinician and scientist Dr. Sue Quaggin present her findings on endothelial cell signaling more than five years ago, Dr. Marie Jeansson, then finishing her PhD in physiology at the University of Gothenburg in Sweden, knew that she wanted to conduct post-doctoral studies in the Quaggin lab at the Lunenfeld.
“I was intrigued by Sue’s renowned expertise in using novel transgenic mouse models to explore the pathophysiology of diseases, specifically those pertaining to the vasculature system,” says Dr. Jeansson. “It has been an incredible opportunity to train in her lab and among the skilled team at the Lunenfeld.”
Since joining the Institute in 2006, Dr. Jeansson has focused her studies on the role of endothelial cells in health and disease, as well as vascular endothelial growth factors using mouse models.
Endothelial cells are the building blocks of our vascular systems and their dysfunction is a hallmark of illnesses including diabetes, kidney disease, malaria, as well as in cardiovascular diseases. Dr. Jeansson and others in the Quaggin lab have been exploring the role of angiopoietin proteins in the vasculature during development and in response to injury.
Last year Dr. Jeansson was the first author of a paper published in the Journal of Clinical Investigation showing how the body defends against damage to the vascular system, and reporting the novel discovery of a protective effect of angiopoietins in illnesses such as diabetes. Specifically, the research elucidated a new role for the growth factor angiopoietin-1 (Angpt1)—a discovery that may lead to the development of new strategies to improve therapies for diabetes, cancer and malaria.
Previous research has shown that certain illnesses including diabetes are characterized by pathologic angiogenesis, as well as altered levels of angiopoietins. Such vascular damage can lead to severe and life-threatening complications including diabetic nephropathy, the leading cause of kidney disease in North America. But no research to date had determined whether there is a functional role for these proteins in the development and progression of illness.
“Our research was the first to show that Angpt1 protects the vascular system against fibrosis, and safeguards against tissue injury and microvascular disease in diabetes, for example,” says Dr. Jeansson. “Angpt1 functions like the brakes in a car—required to stop a moving vehicle but redundant in a stationary one.”
Results of the study showed that Angpt1 is critical for blood vessel growth and development of the heart during fetal development, but is essentially dormant during normal adulthood. The protein only exerts its protective effects over the vascular system once an illness that causes vascular ‘stress,’ such as diabetes, develops. In the absence of Angpt1 and in the case of diabetes, for example, the uncontrolled blood vessel growth and scarring of the vascular system can lead to kidney damage and kidney failure.
Dr. Jeansson’s research— and other projects in the Quaggin lab including studies of angiopoietin-2 as well as the tyrosine kinase receptor for these proteins, Tek—may help clinicians develop more effective means for earlier detection and patient risk stratification, as well as improved therapies. “Manipulating the Angpt1 pathway may have less systemic side effects and may be more tolerable for patients than other anti-angiogenic agents that target factors such as VEGF, which appear to be more essential in healthy blood vessels,” she notes.
In recognition of Dr. Jeansson’s innovative and impactful research efforts, she was recently made a Venture Sinai Fellow (among the Venture Sinai Women group).
Although Dr. Jeansson plans to continue her research into endothelial cell dysfunction in fibrotic diseases, future work in this area may take her back to Sweden, where she hopes to start her own lab next year.
“I am very excited about starting my own lab but will dearly miss colleagues and friends at the Lunenfeld,” says Dr. Jeansson.
Some of the limitations of current anti-angiogenic medications lie in their non-specific actions on healthy cells as well as tumour vasculature. These actions may lead to side effects including kidney damage, hypertension, ulcers, severe headaches and stroke. Researchers in the Quaggin lab are identifying ways to develop new therapies that selectively suppress blood vessel formation in diseases such as diabetes, without damaging health tissues.