Faces of the MRM – Terry Hébert
Meet the minds behind the science – MRM members share their journey, passion, and vision for the future of regenerative medicine.
This interview series is brought to you by the MRM Trainee Committee.
Name: Terry Hébert
Department: Pharmacology & Therapeutics
Hometown: Windsor, Ontario
Lab website: Hébert Lab
LinkedIn: Terry Hébert; X: THebertMcGill
Interview hosted by Diego Loggia.
Can you tell us a bit about your background and your current role at McGill?
I did my BSc and my MSc at the Univeristy of Windsor in Biological Sciences and my PhD at the University of Toronto in the Department of Medical Genetics. After a postdoctoral stage at the Université de Montréal, I took up an academic position at the Montréal Heart Instiute, from there I came to McGill in 2005. I am a professor in the Department of Pharmacology and Therapeutics. I was appointed as Assistant Dean for Biomedical Sciences Education, Faculty of Medicine and Health Sciences, a role I have held since June 2018. I am also the Director of the McGill Regenerative Medicine Network Faculty of Medicine and Health Sciences, a role I have held since January 2022.
What motivated you to pursue a career in regenerative medicine or stem cell research?
Regenerative medicine (RM) became a major thrust in the Faculty of Medicine and Health Sciences at McGill University. The Dean of Medicine expanded commitment to stem cell research in the Faculty of Medicine by including this crucial area in the priorities of the Faculty Strategic Plan. Since the creation of the McGill Regenerative Medicine (MRM) Network, my aim has been to expand stem cell-based research and acquire innovative basic and translational infrastructure to do this at McGill. From organoids and iPSC-derived patient tissue banking to basic and pre-clinical applications, these advances in our collective infrastructure, map a strategic course toward expanding and strengthening our diverse and complementary research programs. We undertook the mission to set McGill onto the world regenerative medicine stage.
Were there any key moments or mentors that shaped the path of your career?
I have been lucky enough to have several excellent mentors both in terms of research and teaching. My PhD supervisor, Rob Dunn, was the most rigorous molecular biologist our country ever produced. I thought of him as a hard ass at the time, but when I look back I learned so much from him. During my postdoc, my supervisor was Michel Bouvier, who gave me the opportunity to get involved in research of GPCRs. The rest, as they say is history. In terms of teaching Radan Capek and Peter McLeod helped me become a better educator than I ever imagined. Another opportunity to learn how to teach came when Marcy Slapcoff invited me to join the Inquiry Network, a TLS (Teaching and Learning Services) run group thinking about how to merge research and teaching. For a long time, I was highly involved with TLS, helping develop strategies to get students to use writing to learn and to develop scholarly habits. I think I have been able to manage the three sides of my career at McGill (Research, Service and Teaching) by integrating them! I have tried to do this at all levels of teaching at McGill. Incorporation of research into teaching is a key part of my teaching efforts at every level.
What are some of the key research areas you’re currently exploring?
My research program is centered broadly around the theme of G protein-coupled signal transduction systems. I am interested in 1) basic mechanisms of how these signalling systems are wired and assembled, 2) novel signalling complexes and pathways associated with alternative subcellular localization of GPCRs and G proteins, 3) the roles that these architectural features of signalling complex design might play in cardiovascular disease, pre-term labour, cancer and a rare neurodevelopmental disease and 4) the development of biosensors that track GPCR and G protein signalling as well as GPCR conformational dynamics in living cells with a new focus on using the biosensors in inducible pluripotent stem cell-based models of disease and in in vivo applications (the latter in the context of Parkinson’s Disease (PD). My research would lead efforts to develop stem cell-based models for drug discovery, to help position McGill University at the forefront of this research. There are few other researchers in the world who have combined signalling and conformational biosensor platforms for GPCRs with stem cell-based models of disease.
What do you enjoy most about teaching and mentoring students?
Teaching is something I enjoy immensely. It usually provides the opportunity to explore a subject together as colleagues and can even invert the usual student/teacher relationship. I learn a great deal in preparing for and giving lectures. I think it is critical to involve the students as much as possible and to draw them out without evoking undue levels of stress in the smaller and more intimate class settings. Training students for careers in research is something that I take very seriously as well- although these days we must prepare them for other careers as well. I always assume, until the person tells me differently, that my trainees intend to pursue academic careers. Thus, we not only have to teach them how to think about and perform experiments, but also how to write, how to present and defend results and how to teach.
I also love designing new courses and programs. I designed and run two graduate certificate programs- Graduate Certificate in Stem Cells and Regenerative Medicine and the Graduate Certificate in Biomedical Science Translation (see here). I developed the Graduate Certificate in Biomedical Science Translational Research which spans 1.5 years and enriches basic science training through a mix of medical style coursework crafted for graduate students, an immersive clinical experience, and engagement with the broader translational network at McGill. It is run out of the Department of Pharmacology and Therapeutics. The coursework starts in the winter semester with an existing course I developed at McGill: Foundations of Translational Science (FMED 525). In the following year, students enrol in a new year-long Fundamentals of Disease Therapy course, PHAR 522, in which clinicians are invited to teach 3-week modules covering one organ system-normal function, associated diseases, and state-of-the-art treatment approaches. Concurrently, students will be paired with clinical mentors in our other new course- PHAR 524 Clinical Mentorship designed for graduate students. Moreover, we organize networking events with clinical mentors, industry partners and MD and MD-PhD students which are essential to fostering a strong interdisciplinary community. I am a co-developer of a new synthetic biology course (BIOT 302) and an advanced lab course in Pharmacology (PHAR 590).
How has stem cell research evolved over the years at McGill?
The mission of the McGill Regenerative Medicine (MRM) Network is to nurture basic and clinical stem cell and regenerative medicine programs at McGill. We now have more than 140 investigators and over 350 active members with broad expertise ranging from embryonic, iPSC and adult stem cells, developmental biology and organoids, disease models, cell-based and small molecule therapeutics to tissue bioengineering. We also have an ethics unit thinking about how best to use the science. Our members come from over 25 different departments, 5 McGill faculties and 5 different Research Institutes of affiliated hospitals. Together, our research output places McGill among the top three Canadian universities in regenerative medicine research. We pursue the development of innovative technologies to manipulate and apply stem cells for regenerative medicine. Our goal is to apply current knowledge and technologies to launch clinical trials, private-sector partnerships and multidisciplinary collaborations. We prioritize activities that expand the legal and ethical bases for guiding and communicating MRM research and its societal contributions.
How do you see stem cell research advancing in the near future, and what role does McGill play in that progress?
Building capacity for developing and testing new cell therapies. Today, current Good Manufacturing Practice (cGMP) is an integral part of the production of any commercial biopharmaceutical product, involving multi-level layered checkpoints to prevent unintended manufacturing errors that ordinary quality control interventions cannot eliminate. It is used to identify and remove sub-standard batches or those that do not reach desired quality. The need for cGMP is critical to market pull for life-saving medicines and biological products, especially in the face of future pandemics. We propose expanding this training into hands-on experience in producing live cell products in an operational clean room setting. The U.S. Food and Drug Administration recently stated its intention to progressively move away from animal testing (Modernization Act 2.0) and rely more on human models such as organoids3. In 2023, Canada took a step in this direction with Bill S-5. The future of biomedical research, and its clinical and commercial translation, depends on humanized models relevant to patients. Organoids (self-organized 3D microtissues generated using human cells) reproduce many aspects of human organ architecture, function, and dysfunction. Our cGMP Development and Training Centre, called MATREC, will create unique new capacity. I played a key role (as the director of the McGill Regenerative Medicine Network (MRM)) in the development of the McGill Advanced Therapies Research and Education Centre (MATREC), which was recently approved as a core platform on campus, serving as a facility for training learners and de-risking potential advanced therapies. MATREC will use an existing cleanroom at the McGill Genome Centre to facilitate the development of skills required to work under current good manufacturing practices (cGMP). As part of its mission, MATREC will provide training, expertise and space for developing ATPs to students, staff and researchers. The facility is based on an operational ISO7 clean room currently used for clinical-grade cell handling on the McGill downtown campus will be dedicated fully to cGMP training and workflow development. Our work helps build an ecosystem around biomanufacturing, disease modeling, and therapeutic development. We build on Canada’s distinctive strengths in stem cell research, through established and emerging private partners in this sector, to drive concrete applications for pandemic preparedness. We support home grown enterprises working on regenerative and precision medicine. Our platform is at the forefront of technology innovation to accelerate regulatory approval of therapeutics.
Building toward clinical trials in a dish. Replacing animal studies and early first in human pilot trials with studies done using patient-derived immune cells and inducible pluripotent stem cells (iPSC)-derived models of cells and tissues is an idea whose time has come. We propose to test established drugs to validate existing clinical trial data and test the power of our platform by expanding into RNA-based medicines to modify CAR-T cells and a disease-in-a-dish model of dilated cardiomyopathy. Lastly, we will expand into using our approach to study disease progression in a rare neurodevelopmental disorder, establishing its utility to test therapies for this and other rare diseases. Further, the development of a biobank of iPSC lines which reflects the diversity of the Canadian population from both control subjects and from patients suffering from different diseases at various stages would be a tremendous resource from which to undertake disease modelling, drug screening and trials for therapeutic effects. Such a resource, paired with modern screening, disease modeling technologies and genomic characterization will be invaluable for the development of next generation therapeutics. This is a critical step to achieve precision and personalized medicine in more broadly inclusive manner. Here, we propose a program of research to build a unique drug discovery platform, based on patient-derived iPSCs, centered on a rare disease, a common disease and immune cell therapies. To optimize the translation of therapeutic approaches, we need a richer and more complete understanding of disease, achievable only by using authentic, “real-world” models derived directly from patients. One day, our program will revolutionize preclinical and clinical modelling for drug development by establishing the infrastructure to generate preclinical models using iPSCs, cell engineering and recent advances in organoids, cell-derived 3D organotypic models that permit the study of biological processes and the responses to drugs. By linking these approaches with novel biosensor-based drug screening technologies, our programs feed disruptive development of personalized treatment to improve outcomes for patients.
What are some of the major challenges facing stem cell research today? How is your team working to address them?
That is a complicated question. A short answer, anchored on my experience at McGill would be this. We need to focus on projects combining modern drug discovery tools with state-of-the-art stem/immune cell and organoid approaches. iPSCs can be grown into a range of organoids using 3D bioprinting approaches, as essential tools in the drug discovery pipeline by stratifying compounds that are more likely to have efficacy in vivo, greatly accelerating the drug discovery process down to the single cell level. These aims would both highlight how the combination of relevant model systems and platforms for nucleic acid-based drug candidates in high-content screening campaigns adds value to our research programs. The Early Drug Discovery Unit (EDDU) at the Neuro and the Heart-in-a-Dish project in the Department of Pharmacology and Therapeutics provide critical venues to link drug discovery with an effort to train, enable and accelerate the development of RNA-based therapeutics. Other considerations are how to switch from a focus on drugs as medication to living therapeutics? That requires us to change what we teach students at all levels.
What advice would you give to graduate students looking to pursue graduate school? How should graduate students typically handle setbacks or unexpected results in their research?
Don’t be afraid of failure. This is how we learn. The first two years of my PhD was one failure after another. There was never a time before or since, when I learned so much. You have to learn how to perform experiments, but also how to write, how to present and defend results and how to teach. You should seek opportunities to do all those things- writing first drafts of manuscripts, reviewing grants and manuscripts, teaching and giving talks are all things that I try and get my students to do. I review a lot of papers and grants so senior students get an opportunity to compare notes with me. As a lab, we have lab meetings and journal clubs so opportunities to present are frequent. I also encourage my students and post-docs to attend and present at least one national or international meeting per year. I believe these skills and habits must be learned as early as possible- thus undergraduate research trainees are effectively exposed to many of the same opportunities. Also, think about where you want to be all the time and figure our what you need to get there.
What opportunities are there for graduate students at McGill to get involved in stem cell research, or collaborate with other researchers or institutions in the field of regenerative medicine?
As I said above, the MRM is comprised of more than 140 investigators and over 350 active members with broad expertise ranging from embryonic, iPSC and adult stem cells, developmental biology and organoids, disease models, cell-based and small molecule therapeutics to tissue bioengineering. We also have an ethics unit thinking about how best to use the science. Our members come from over 25 different departments, 5 McGill faculties and 5 different Research Institutes of affiliated hospitals. Find us- and follow your interests.
How do you envision the impact of your research on healthcare and patient outcomes in the next 5 to 10 years?
Medicine is changing… the future of medicine will involve replacing lost tissues and organs using the tools and approaches in the discipline of regenerative medicine. We are moving away from animal models… the future of biomedical research will depend on models more relevant to patients and more ethical in our treatment of animals. Drug discovery is changing… the future of drug discovery and the medicines that follow will be personalized and depend on these new models. The nature of therapies is changing… new therapies will include cells carrying RNAs and other modifications delivered to patients.