3. Major Research Areas

The 21^st century is witnessing the re-emergence of infectious diseases as a major threat to global health. In that respect, the COVID-19 pandemic that began in 2020 has been an all-too-dramatic illustration of infectious diseases as an agent of global catastrophe. Our generation now has first-hand experience that pandemics disrupt entire societies worldwide, challenge public health systems, education, social interactions and the economy. Everyone everywhere has been affected, with the most vulnerable suffering the greatest consequences: many as patients or relatives, with the trauma of critical care, the suffering from unexpected lingering symptoms, the anxiety of the unknown, and the aggravation of social isolation and distress, especially for the elderly, and the fragility of mental wellness, especially within the younger population. The pandemic has also highlighted the dramatic health inequities and chronic vulnerabilities that exist within our society and that must be addressed.

The causes of past and emerging infections’ increasing threats to global health are multifaceted, from the continuous appearance of new and highly virulent pathogens, such as SARS-COV-2, to the increased prevalence of antibiotic-resistance in microorganisms. Antimicrobial overuse, increased globalization, population mobility, and a changing climate all additionally contribute to the growing threat of infectious diseases.

The COVID-19 crisis also revealed the coming-of-age of groundbreaking technologies for the accelerated development of vaccines, enabled and inspired by decades of fundamental research in molecular and structural biology and in other related fields. This new generation of vaccine technologies holds considerable promise of being transferrable to other existing and future threats to our immune systems, throughout Canada and worldwide.

The COVID-19 pandemic has reinforced the notion that faster, increasingly more affordable genome sequencing technology is transforming many sectors of medicine. This includes immunology and epidemiology–from early virus sequencing and tracking of variants to the delivery of new methods of testing and epidemiologic surveillance. The crisis also highlighted the enabling value, but also the challenges, of fast-paced scientific development. On the one hand, early public sharing of the SARS-COV-2 genome accelerated vaccine and test developments at an unprecedented pace; while on the other, early deposition of non-peer-reviewed preprints contributed to confusing statements from “experts” and challenged public trust in the scientific approach. Relatedly, the pandemic has demonstrated the need to engage in interdisciplinary investigations, addressing issues as far-reaching as the psychology of individuals’ responses to the pandemic and to public health measures, vaccine hesitancy, and the political, economic and social implications of health and healthcare.

In parallel, studies of inflammatory and immune responses to infection and tissue injury are providing novel insights and new therapeutic opportunities in major chronic inflammatory disorders ranging from inflammatory bowel disease, multiple sclerosis, arthritis and periodontal disease to asthma, that are major sources of morbidity and healthcare costs in Canada.

In recent years, we have come to better understand the complex relationship between the host and the microbial world around it. We now recognize that the microbiome plays a central role in the programming and regulation of the immune response and is a major determinant of health and disease. This strongly emerging view yields unexpected and intriguing hypotheses of the possible direct or indirect contributions of the microbiome and related systems to major, apparently “remote” syndromes in neurodegenerative, cardiovascular and metabolic diseases.

Since its inception, our SRP has identified Inflammation & Infection as key to the enduring leadership and impact of McGill’s biomedical research. We have fostered efforts built from long-established strengths, taking advantage of the presence of substantial resources in genomics, informatics, epidemiology and population health. For instance, McGill has an established track record in the fields of tuberculosis (e.g., with McGill’s International TB Center), HIV, HPV and other chronic viral diseases, and key parasitic infections such as Leishmania and malaria (e.g., via McGill’s Institute of Parasitology).

McGill will continue to grow its leadership and reputation in the broader domains of Infection & Inflammation, by mobilizing its strengths in core related disciplines and by actively encouraging efforts at their interface, in particular with genomics, biostatistics, bioinformatics (including modeling, biobanking, data science) and with other major research areas such as brain and mental health.

The creation and rapid growth of the McGill Interdisciplinary Initiative in Infection & Immunity (MI4) have reaffirmed the ambition and expanded the scope of McGill’s research in the area of infectious diseases. MI4 now also plays a major coordinating role across McGill’s specialized centres and platforms in this area, including the McGill Centre for Research on Complex Traits, the Centre for Viral Diseases, and the McGill International TB Centre, among others. Another transformative element is the new School of Population & Global Health, which is expected to play a leading role in fostering collaborations and facilitating studies of both major and neglected infectious diseases in Canada and abroad. These new resources also represent enabling instruments to strengthen and coordinate present and future efforts in related key areas such as microbiome research, the development of rapid detection tests of infectious pathogens, and vaccine development approaches against infections and inflammatory conditions.

We encourage all efforts along and between McGill’s current strong pillars of fundamental research using cell and disease models, epidemiologic and translational research, and major clinical research assets at the MUHC (including MI4’s Clinical Research platform) and JGH and in several disease-specific campus and hospital-affiliated centers and units supporting clinical trials (e.g., in connective tissue diseases, chronic inflammatory and autoimmune diseases such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis). We also anticipate a major catalytic effect driven by the planned Institute for Genomic Medicine on McGill’s genomic and epigenomic research and its translation to personalized medicine. Another major asset is the new FRQS Centre for Structural Biology hosted at McGill, as a crucible of multidisciplinary expertise in this and other major research areas.

Immune diseases provide a unique opportunity to deliver on the promise of personalized medicine. Leveraging existing expertise and infrastructure, innovations in models of care, fundamental and translational research, advanced computational methods and implementation science will advance McGill’s international position in this area.

Along the same lines, continued investment in expertise and infrastructure in oral, skin and gut microbiome research at McGill will strengthen the position of our scientists across life science disciplines to reveal how our microbial selves can inform the diagnosis and treatment of diseases from cancer to neurodegenerative diseases.

McGill researchers are encouraged to pursue their work at the levels of molecules, cells, patients, and populations to discover new mechanisms underlying the development of infectious and inflammatory diseases. They aim to advance novel diagnostics and therapies for these conditions and deliver solutions to the populations that need them the most. Areas of research span viral, bacterial, and fungal disease-burden around the world, and include hospital-acquired infections, antimicrobial resistance, and auto-immune and inflammatory diseases.

We have also learned from the COVID-19 crisis that infections can induce complex syndromes affecting other body systems. For instance, primary clinical symptoms (e.g., respiratory distress) may be accompanied by the unexpected emergence of severe neurological events and acute and chronic challenges to mental health. The complexity of such clinical traits induced by new pathogens needs to be acknowledged, reported and studied. In that respect, the constitution for research purposes of high-quality cohorts of widely and deeply phenotyped patients are key to the identification of biological and other determinants of disease developments and response to treatment. Efforts such as the Quebec COVID-19 Biobank spearheaded by McGill’s Canada Excellence Research Chair in Genomic Medicine serve as blueprints for a more global and systematic research approach at McGill, based on large and well-curated patient cohorts, advanced computational approaches from structural biology to epidemiology to truly enable both personalized and societal interventions against infectious diseases. These approaches hold tremendous potential to generalize and transfer to other major disease areas.

Cancer remains a leading cause of premature death in the western world and is now a significant global challenge in the developing world. Improved strategies for cancer prevention and early detection are required, in parallel with fundamental advances. These latter include the better understanding of the complex interactions between deregulated genetics, gene expression and a broad range of environmental and behavioral risk factors of cancer development. These aspects need to be inclusive of biological differences and societal disparities in populations that contribute to cancer risk and response to therapy, which are still poorly understood. Despite significant improvements, our ability to successfully treat many cancers has yet to be fully realized. Even in responders, disease management often requires that the cancer is maintained as a chronic condition over prolonged periods of time, leading to unintended consequences.

The recognition that cancers are highly heterogeneous, including in response to therapies, poses significant challenges for the successful implementation of effective diagnostic and therapeutic interventions. An enhanced mechanistic understanding of genetic and epigenetic changes, of post-transcriptional regulations of gene expression, and of the evolving tumor micro-environment as cells move from pre-malignancy to metastatic cancer is required, especially in demographically diverse populations.

With an aging population in Canada, our health care system must further adapt to the increasing likelihood that individuals will present with multiple chronic diseases and co-morbidities (e.g., metabolic and cardiovascular diseases, diabetes, infection/inflammation, immunodeficiency and obesity) which collectively further impact their lifetime cancer risk. It is therefore imperative that McGill researchers from multiple disciplines join their efforts to increase our understanding of these complex interactions, rather than studying each in isolation. In recognizing this, cancer sits at the intersection with deregulated control of our endocrine, metabolic and immune systems.

The impact that the COVID-19 pandemic has had and will continue to have on the entire trajectory of cancer prevention, treatment, and survivorship must be addressed. We must continue to build on the innovations and disruptive technologies stimulated by the pandemic and lead their integration into a changing health care system to improve the life of all Canadians.

McGill has a strong research community in pediatric and adult oncology, with specific leadership in the basic mechanisms of molecular and cellular cancer pathophysiology, tumor-host interactions, metastatic dissemination, the study of responses and resistance to varied forms of treatments, and in the areas of cancer prevention, cancer genetics, screening, and survivorship. A new research focus has grown in recent years that is reliant on large scale omics-based approaches to integrate our understanding of the pathobiology of cancer with the development of novel markers for refined clinical diagnosis and identification of new therapeutic targets. Cancer research across the McGill ecosystem has enhanced an integrated focus on the patient experience through the entire disease trajectory with improved screening programs, patient-centric care models, targeted and more efficacious therapeutic and e-health innovations, integrated with patient-reported outcomes.

The first priority in this area will be to increase the coordination of leading-edge fundamental and translational cancer research across the McGill community. To this end, the formation of a McGill Cancer Consortium (MC²) will bring together multidisciplinary research strengths within the entire McGill research ecosystem (see section B). Specific areas of focus for MC² will include: (1) a better understanding of the molecular, genetic and post-transcriptional markers associated with the development of all forms of cancer; (2) improved understanding of cancer risk factors; (3) improved methods for screening and early detection; (4) understanding the mechanisms of metastatic spread to specific organs; (5) understanding therapeutic resistance and how it can be overcome ; (6) elucidating how an evolving tumor microenvironment contributes to emerging forms of hard-to-treat/resistant cancers and (7) helping cancer patients and their families deal with psychological, emotional and social issues related to the diseases.

The second priority for McGill’s cancer research is to advance personalized cancer interventions focused on cancer vulnerabilities via inherent genetic risk factors, metabolic programming, immuno-profiling, epigenetic alterations, proteogenomics and patient-derived models, including biological material from cancer clinical trials. Coordination between the new McGill Cancer Consortium and McGill’s Genomic Medicine experts will be encouraged. The study of these novel approaches also needs to engage McGill’s strengths in structural biology, digital and molecular pathology and immunoprofiling, computational models and bioinformatics, and population health research. McGill’s clinical trials infrastructure is a current asset but will also need to anticipate and adapt to new treatment technologies on the horizon and promote clinical translation of McGill discoveries.

The third priority is to mobilize psychosocial oncology and health services research to enhance the experience of patients coping with arduous treatments and taxing side effects while supporting their families. In this respect, the involvement and coordination across all Schools, the new Institute of Health Sciences Education and other McGill strengths in patient engagement studies, patient outcome measures and research on health sciences education are encouraged. These strengths and others will also advance population health research on cancer prevention as a priority.

The sustained growth of McGill cancer research, notably via clinical and prevention trials, requires the collaboration, coordination and cooperation between our campus-based scientists and researchers and healthcare units across our affiliated hospitals (Cedars Cancer Centre and the Cancer Research Program and the RI-MUHC, the Brain Tumor program at The Neuro, the Segal Cancer Centre at the Jewish General Hospital, the cancer program at St. Mary’s Hospital) and relevant research centres and platforms (Rosalind & Morris Goodman McGill Cancer Institute, the McGill Centre for Translational Research in Cancer, CRP-MUHC, the Interdisciplinary Oral Health clinical research platform at the Montreal General Hospital and the Department of Oncology). In this respect, the Rossy Cancer Network (RCN) is an asset for clinical coordination that needs to be leveraged, for the harmonization of treatment strategies and the reporting of outcome measurements, across all McGill teaching hospitals and the Réseau Universitaire Intégré de Santé et Services Sociaux (RUISSS). The RCN also strengthens McGill’s efforts in psychosocial oncology, health services research, palliative care and related fields. The Department of Oncology will continue to play a pivotal role, leveraging the RCN to assist this enterprise.

As for all our key research areas, cancer research will benefit enormously from the advent of large and well-curated diverse patient cohorts linked with clinical trials and real-world evidence, epidemiological studies, robust clinical data, therapy response and patient outcomes. These resources must be supported by data-driven and other computational modeling approaches, including artificial intelligence and other data-driven technology for healthcare and health research. With a large and diverse patient basin and proactive coordination across units, McGill cancer researchers and clinicians are well poised to advance their leadership in this area as well as address disparities in cancer outcomes with respect to multi-disciplinary research opportunities (from genes to society) which includes ‘barcoding’ a cancer patient’s genome for research and individualized care across their lifespan. Here too, data readiness in terms of joint vision, organization and infrastructure will be key for the McGill cancer community to participate in and leverage major opportunities for multicentric collaborations and platform developments for data analytics, such as via the pan-Canadian Digital Health & Discovery Platform (DHDP) funded by ISED in participation with the Terry Fox Marathon of Hope Cancer Centres Network.

Cancer research contributes strategic value to McGill’s efforts aimed at addressing the global health agenda. In close partnership with the new School of Population and Global Health, the Department of Oncology has launched a Task Force on Global Oncology, which has brought together our assets in this area. Our efforts will be articulated with this Task Force to lead international collaborations to expand opportunities for large-scale translational studies and capacity building.

Although considerable progress has been made in the management of stroke and other acute brain injuries, chronic diseases of the nervous system remain a major source of morbidity in all age groups. Central nervous system disease also manifests itself as severe neurological and psychiatric disorders, which account for an enormous burden of disease. With an aging population, the prevalence and burden of neurodegenerative diseases are major concerns for a growing number of patients, their families and the healthcare system at large. Finally, and as noted above, the COVID-19 pandemic will have enduring repercussions on mental health, whose nature and incidence are hard to anticipate presently. Acute and chronic pain, with the opioid crisis as well as other forms of addictions also have considerable individual and societal consequences that challenge health care systems.

Relative to other major disease areas and despite decades of efforts, including major clinical trials, most brain and mental health disorders still have limited therapeutic options. A consequence and concerning trend are the withdrawal of several pharmaceutical companies from neuroscience research and development, which has shaken the landscape of industry-sponsored research in the field, but may also represent opportunities for new models of industry partnerships to emerge.

These current challenges require a better understanding of the underlying neurobiology at the molecular, cellular and systems levels, and in relation to complex symptoms and behavior, the development of objective disease markers, and the improvement of rehabilitation strategies and models of care delivery that better take into account the needs of patients and their families.

McGill has adopted a unified approach to chronic brain disease, bringing together psychiatry, neurology, rehabilitation sciences and related clinical disciplines such as nursing and family medicine.

Key aspects of neuroscience and mental health research at McGill, including new faculty recruits, cross-cutting platforms and innovation programs, have been enabled over the past 3 years via the transformative award from the Canada First Research Excellence Fund, entitled “Healthy Brains, Healthy Lives” (HBHL), and a number of large disease-specific philanthropic initiatives in this area. The new research resources enabled by these programs – e.g., HBHL’s NeuroHub portal, the early drug discovery platform at the Montreal Neurological Institute and Hospital (collectively, The Neuro), the open-science practices promoted by the Tanenbaum Open Science Institute (TOSI) at The Neuro – are expected to reach maturity by 2025. With sustainable models of operation and appropriate performance indicators, especially of their adoption and actual impact, they are expected to build capacity for dissemination across other units and disciplines.

McGill has historical and renewed strengths in neuroscience: in particular imaging techniques and their applications to radiology, clinical trials, cognitive sciences and neuropsychology; the genetics of common and rare neurological diseases and the view of neurological and psychiatric syndromes as a continuum; neural circuits, networks and neuronal signaling studied at multiple scales, and the development of transgenic models of complex disease traits. Major research themes in neuropsychiatry include Alzheimer’s and other forms of dementia, environmental adversity, neurodevelopment, youth mental health and early intervention, sleep and biological rhythms, stress, anxiety, depression, and suicide. New forms of treatments of neuropsychiatric disorders using neuroplasticity-inducing pharmacotherapies and paradigms of psychedelic-assisted therapies are also promising avenues of research that can mobilize a large diversity of McGill expertise.

The Neuro, via new enabling programs in autism (ACAR) and open science approaches from TOSI, and the Douglas Mental Health University Institute and its new research organization are major players in these efforts. They already form a nucleus in fundamental and clinical neuroscience research, and will increase their interactions further in specific aspects of neuroimaging, biobanking and related data science approaches. The growing experience at the Neuro and the Douglas with large, multimodal research data repositories–covering complex issues around consenting patient participants for data sharing, framing data access and sharing policies and enabling new forms of partnerships with industry–will be essential to the strategic goal of building research cohorts across our research network, in a concerted and consistent manner. Future related projects need to build and learn from these early efforts and be inclusive of the diversity of perspectives and specific needs of research users to specify the best possible data management tools.

The neuroscience community at McGill also includes other major centres of expertise and clinical-research integration within the Brain Repair and Integrative Neuroscience Program at the RI-MUHC, the Alan Edwards Centre for Research on Pain as well as in cognitive neuroscience in the Centre for Research on Brain, Language & Music.

Demographic pressures and the continuing improvement of acute illness treatments have made wellness in aging and the management of chronic diseases major challenges. Healthy aging, with maximum autonomy, over a prolonged life expectancy is a societal priority. In parallel, important advances and reflections around palliative care and end-of-life have raised awareness of individuals and society. Age-related illnesses often induce different forms of cognitive decline and physical disability in a growing proportion of our aging population. Disability can also be congenital or acquired during the life-course, in the form of physical, sensory, cognitive or mental impairments accompanied by diminished health and reduced quality of life, limitations in daily activities and social withdrawal. Such impairments bear significant physical and mental health consequences for the affected individuals, their families and society at large. More broadly, risk factors such as smoking, diet and obesity, physical inactivity and poor nutrition have an overwhelming negative impact on health at any point in time across the lifespan.

Managing developmental and chronic conditions across the lifespan is complex: it requires a multidisciplinary approach to prevention before and after birth, treatment and repair, and the development of optimized management (including self-management) strategies with effective health and social policies. Our Faculties feature a solid research portfolio of catalyzers and enablers to address these complex questions. They include the School of Nursing, the School of Communication Sciences & Disorders, the School of Physical & Occupational Therapy, and the new School of Population & Global Health. Our Faculties also encourage all forms of partnership among the Schools, clinical departments, specialized divisions and patient organizations. These concerted, trans-disciplinary efforts aim to foster the development and implementation of approaches to improve individual prevention and promote social awareness, advance quality of care, solutions and policies to adapt physical environments, and encourage the development and utilization of measurable patient outcomes. We will promote such research efforts around the critical life periods of gestation and early development, as well as in aging and associated degenerative and chronic diseases; a focus on functional (re)habilitation will also be encouraged and developed.

Developing interdisciplinary strategies and strong potential for influencing institutional policies and clinical practice to prioritize prevention, self-management and modification of behaviors, needs to engage all elements of the community in participatory research and action processes: from health professionals to families, educators, and neighbors. The participatory research group in Family Medicine and at the Ingram School of Nursing will coordinate around this effort. The inclusion of vulnerable populations in related studies and participatory research approaches is essential to maximize the significance and impact of research and knowledge translation outcomes.

McGill will continue to build on research excellence in endocrine and metabolic disorders (e.g., diabetes, osteoporosis, bone and tooth demineralization and calcium homeostasis disorders) and on the comorbid factors that affect wellness spanning the lifetime.

In cardiovascular health, McGill will focus its efforts where it can make distinctive contributions e.g., in congenital heart disease, in hyperlipidemia, atherosclerosis and thrombosis (including vascular calcification), and in hypertension. Emphasis will be placed on the study of immune regulation, risk factors, and impact of behavioral interventions for prevention of cardiovascular risks.

Pain is a significant comorbidity of chronic conditions; awareness about chronic pain as a debilitating, chronic syndrome in itself has grown substantially. With the Canada Excellence Research Chair in Pain Research and new leadership at the Alan Edwards Centre for Research on Pain, the Faculties encourage research efforts on the biological mechanisms of pain, with a particular emphasis on chronic pain and comorbidities affecting mental health. Efforts in this domain also have multidisciplinary facets and will need to bring together clinicians, hospital-based researchers and basic scientists from several departments and divisions.

Research on pain and other mental and physical disabilities caused by trauma will also be encouraged. Improving our ability to both detect and repair related injuries is also a priority area. Trauma research needs to involve innovative diagnostic tools with advanced medical imaging and neuropsychological testing, new surgical approaches in multiple disciplines, emphasizing the role of simulations in medical training, the development of artificial limbs and brain/body-computer interfaces and related technology for patient training and physical rehabilitation, and stem cell and other approaches to regenerative medicine. We emphasize that all these research segments are also pertinent to the other strategic priority areas in our Faculties.

Healthcare Across the Lifespan will mobilize McGill’s expertise in health-outcomes and patient-oriented research and encourage joint efforts with other strategic fields such as genomics, cognitive neuroscience and mental health to develop a more holistic approach of these complex conditions. With this patient-first approach, research and deployment of new technologies will need to be leveraged for all stakeholders. For instance, new tools and apps for patient empowerment such as OPAL[1] developed by researchers at the MUHC have tremendous potential to establish a fruitful feedback loop between patient information and orientation in the clinic, secured and informed patient data collection for research purposes, and the personalized adjustment of clinical interventions.

Research will be extended to community-based clinical settings, permitting large-scale translational research programs that will ultimately promote wellness and better health outcomes across the lifespan. St. Mary’s Research Centre has a leadership role to play in that area. Using an interdisciplinary approach with diverse strengths in Medicine (Internal Medicine, Family Medicine, Epidemiology, Nursing, Physical and Occupational Therapy, Psychiatry) and Dentistry, McGill will collaborate with the healthcare system to build on established excellence in participatory and health outcomes research with an emphasis on knowledge translation and implementation sciences.