FACE TO FACE with Dr. Stéphane Laporte, a scientist who champions the incredible power of basic science to shape the future of medicine

- Medical scientist, Experimental Therapeutics and Metabolism Program, Research Institute of the McGill University Health Centre (RI-MUHC)

- Director, Molecular Imaging Core facility at the RI-MUHC

- Professor and Director of Research, Division of Endocrinology and Metabolism , McGill University

June 25, 2015

Source: MUHC. Professor Stéphane Laporte's career as a pharmacologist has been, to say the least, extremely successful. He trained as a PhD student at the Université de Sherbrooke, Quebec, and then as a postdoctoral fellow at Duke University, USA, working with Dr. Marc Caron and his collaborator, 2012 Chemistry Nobel Prize winner Robert Lefkowitz. He has developed an expertise in a class of cell receptors involved in all physiological responses. He is also world-renowned for his knowledge of allosteric drugs, a new class of molecules capable of treating diseases in a safer and more refined way. In 2010, he "hit the jackpot" as he likes to say, when an allosteric drug he helped characterize in collaboration with chemist Dr. William Lubell and other researchers from the Université de Montréal and McGill University showed potential to prevent preterm birth, a common and serious problem for newborns' health. Also in collaboration with researchers the Université de Montréal, his lab developed innovative biosensor technology now licensed to a biopharmaceutical company. Professor Laporte is currently studying mechanisms to improve drug action in cardiovascular diseases.

Your expertise in molecular pharmacology is recognized worldwide. You specialize in a class of receptors called G protein-coupled receptors, or GPCRs. What are they? 

GPCRs are proteins embedded within the plasma membrane of cells, and their role is to transfer a signal from the external environment into a cellular response. They're involved in many physiological responses such as contractions of the heart or the uterus, control of blood pressure, release of glucose and even our capacity to see, taste or smell. 

How does that signalling happen?

When a hormone circulating in your blood recognizes a receptor, it will bind to it and trigger a response. Hormones can engage different signalling pathways thus leading to different responses. Many diseases evolve because receptors don't always respond properly. In hypertension and congestive heart failure, for example, the response is too high. One way to treat these diseases is to act at the receptor level and block it. My lab specializes in receptors in the cardiovascular system called angiotensin type 1 receptors. 

You are also internationally recognized for contributing to the improvement of drug action through biased signalling. What is that?

Biased signalling allows us to modify the cell's usual response to stimulation by giving priority to certain signalling pathways. We are developing a new class of molecules called biased allosteric drugs. Unlike conventional drugs, they target sites outside of the normal hormone-binding site on the receptor and act in a selective, safer and more refined way. Pharmaceutical companies are now re-testing their own drugs and screening them for their potential for allosteric bias property. This research can contribute to the advancement of personalized medicine, because the more we understand bias signalling, the more we can create tailored medications for patients, which we know do not always respond equally to the same drug.

In 2010, you developed a drug in collaboration with researchers from the Université de Montréal and McGill University that could one day be used to treat premature labour, with fewer side effects.

Preterm birth is responsible for 75 per cent of all newborn deaths in babies without birth defects. We developed a molecule that binds to a GPCR and connects to only one specific signalling pathway, blocking uterine contractions. The drug is undergoing clinical trials in women with dysmenorrhoea (painful uterine contractions during menstruation). We hope that eventually the next generation of this drug can be developed and tested in pregnant women. 

How do you feel about having participated in the development of this new drug with so much positive potential?

It's the chance of a lifetime. As a pharmacologist, it's rare to be involved in all phases of the development of a drug: designing a small molecule, testing it in vitro, in a preclinical model and seeing it go to clinical trial. This process can take twenty years sometimes, so I'm proud having accomplished that early on in my career.

Do you feel pressure as a basic scientist to explain the significance of what you do?

Absolutely. Some people think that if a drug works clinically, you don't really have to understand how it works. Well, if we don't understand how molecules work, we are dependent on luck to improve drug action, increase patient lifespan or find a cure for diseases such as diabetes, hypertension or congestive heart failure. That's why basic research is fundamental.

You trained at Duke University as part of a world-renowned group of researchers, one of them was Robert Lefkowitz, a Nobel-prize winner. How has that experience influenced your career? 

It was a wonderful environment and a life-changing experience. I was under the supervision of Dr. Marc Caron, a researcher from Quebec who collaborated with Dr. Lefkowitz. These high-profile researchers discovered GPCRs and specialized in their pharmacology. Training in that environment gave me visibility and helped establish my reputation as an expert in my field.

How do you see your role with your trainees?

Teaching in my lab is the thing I'm proudest of. It's gratifying to help students evolve and to see them come up with their own ideas. I teach them the importance of honesty, hard work and perseverance and I try not be patronizing. I also tell them to always remain curious.

Besides your work as a researcher, you're a professor at McGill University and the director of the Molecular Imaging Core facility at the RI-MUHC. How do you balance all that and your family life?

Like my colleagues, I wear many hats:  I do research, train students, give conferences, work on committees, review grants, and that can be overwhelming sometimes. But for me, science is not work, it's a way of living. I ask myself research-related questions all the time. Furthermore, my wife is also a scientist – she's a pharmacologist and a professor at the Université de Montréal – so science is never far.
 

Listen to the interview with Dr. Stéphane Laporte (in French) presented by the Canada Foundation for Innovation (CFI). Dr. Laporte talks to us about his fields of interest and the thrill of working in the research arm of an institution that is at the forefront of health care.