Morgan Craig

Morgan Craig
Université de Montréal | UdeM · Department of Mathematics and Statistics

PhD (Pharmaceutical sciences); MSc (Mathematics)

About

84
Publications
9,696
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,359
Citations
Additional affiliations
January 2020 - present
CHU Sainte-Justine
Position
  • Researcher
June 2018 - present
Université de Montréal
Position
  • Professor (Assistant)
March 2016 - May 2018
Harvard University
Position
  • PostDoc Position
Education
September 2011 - March 2016
Université de Montréal
Field of study
  • Sciences pharmaceutiques
September 2009 - August 2011
University of Manitoba
Field of study
  • Mathematics
September 2003 - May 2006
Université de Saint-Boniface
Field of study
  • Mathematics

Publications

Publications (84)
Preprint
Full-text available
Glioblastoma is the most aggressive primary brain tumour, with a median survival of just fifteen months with treatment. Standard-of-care (SOC) for glioblastoma consists of resection followed by radio- and chemotherapy. Clinical trials involving PD-1 inhibition with nivolumab in combination with SOC failed to increase overall survival. A quantitativ...
Article
Full-text available
Glioblastoma is the most common and deadliest brain tumour in adults, with a median survival of 15 months under the current standard of care. Immunotherapies like immune checkpoint inhibitors and oncolytic viruses have been extensively studied to improve this endpoint. However, most thus far have failed. To improve the efficacy of immunotherapies t...
Preprint
Full-text available
The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in millions of deaths globally. Adults with immunosuppression (e.g., solid organ transplant recipients) and those undergoing active cancer treatments experience worse infections and more severe COVID-19. It is difficult to conduct clinical stud...
Article
Full-text available
Mathematical modelling applied to preclinical, clinical, and public health research is critical for our understanding of a multitude of biological principles. Biology is fundamentally heterogeneous, and mathematical modelling must meet the challenge of variability head on to ensure the principles of diversity, equity, and inclusion (DEI) are integr...
Chapter
Full-text available
Combination therapies are fundamental to cancer treatments, including in breast cancer, which is the most common invasive malignancy in women. Breast cancer treatment is determined based on molecular subtypes. Since 2016, combination palbociclib and fulvestrant has been used to treat hormone receptor-positive breast cancer. However, the impact of h...
Article
Full-text available
On July 19th, 2023, the National Institute of Allergy and Infectious Diseases co-organized a workshop with the Society of Mathematical Biology, with the authors of this paper as the organizing committee. The workshop, “Bridging multiscale modeling and practical clinical applications in infectious diseases” sought to create an environment for mathem...
Article
Full-text available
Throughout the SARS-CoV-2 pandemic, several variants of concern (VOCs) have been identified, many of which share recurrent mutations in the spike glycoprotein’s receptor-binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypo...
Preprint
Ovarian cancer is commonly diagnosed in its late stages, and new treatment modalities are needed to improve patient outcomes and survival. We have recently established the synergistic effects of combination tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and procaspase activating compound (PAC-1) therapies in granulosa cell tumours...
Article
Full-text available
The development of new cancer therapies requires multiple rounds of validation from in vitro and in vivo experiments before they can be considered for clinical trials. Mathematical models assist in this preclinical phase by combining experimental data with human parameters to provide guidance about potential therapeutic regimens to bring forward in...
Article
Full-text available
Objectives Identifying biomarkers causing differential SARS‐CoV‐2 infection kinetics associated with severe COVID‐19 is fundamental for effective diagnostics and therapeutic planning. Methods In this work, we applied mathematical modelling to investigate the relationships between patient characteristics, plasma SARS‐CoV‐2 RNA dynamics and COVID‐19...
Preprint
Full-text available
B cells and antibodies are crucial in protecting against infections like SARS-CoV-2. However, antibody levels decline after infection or vaccination, reducing defences against future SARS-CoV-2 infections. To understand antibody production and decline, we developed a mathematical model that predicts germinal center B cell, long-lived plasma cell, m...
Chapter
Virtual clinical trials (VCTs) have gained popularity for their ability to rationalize the drug development process using mathematical and computational modelling, and to provide key insights into the mechanisms regulating patient responses to treatment. In this chapter, we cover approaches for generating virtual cohorts with applications in cancer...
Article
Full-text available
Glioblastoma is the most common and deadly primary brain tumour in adults. All glioblastoma patients receiving standard-of-care surgery-radiotherapy-chemotherapy (i.e., temozolomide-TMZ) recur, with an average survival time of only 15 months. New approaches to the treatment of glioblastoma, including immune checkpoint blockade and oncolytic viruses...
Preprint
Full-text available
Combination therapies are fundamental to cancer treatments, including in breast cancer the most common invasive malignancy in women. Breast cancer treatment is determined based on molecular subtypes, and since 2016, combination palbociclib and fulvestrant has been used to treat hormone receptor-positive breast cancer. However, the impact of heterog...
Article
Full-text available
Heart failure (HF), which is a major clinical and public health challenge, commonly develops when the myocardial muscle is unable to pump an adequate amount of blood at typical cardiac pressures to fulfill the body’s metabolic needs, and compensatory mechanisms are compromised or fail to adjust. Treatments consist of targeting the maladaptive respo...
Article
We consider a general mathematical model for protein subunit vaccine with a focus on the MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2, and use the model to study immunological outcomes in the humoral and cell-mediated arms of the immune response from vaccination. The mathematical model is fit to vaccine clinical trial data. We el...
Article
Full-text available
The COVID-19 pandemic has revealed the need for the increased integration of modelling and data analysis to public health, experimental, and clinical studies. Throughout the first two years of the pandemic, there has been a concerted effort to improve our understanding of the within-host immune response to the SARS-CoV-2 virus to provide better pre...
Article
Full-text available
The lipid nanoparticle (LNP)-formulated mRNA vaccines BNT162b2 and mRNA-1273 are a widely adopted multi vaccination public health strategy to manage the COVID-19 pandemic. Clinical trial data has described the immunogenicity of the vaccine, albeit within a limited study time frame. Here, we use a within-host mathematical model for LNP-formulated mR...
Article
In recent years, artificial intelligence (AI) has played an ever-increasing role in research across the physical sciences and beyond. In this Voices piece, published as part of the Cell Reports portfolio joint special issue on AI in healthcare, we ask a panel of experts: How do you think AI will change drug discovery?
Preprint
Full-text available
Throughout the SARS-CoV-2 pandemic, several variants of concern (VOC) have been identified, many of which share recurrent mutations in the spike protein's receptor binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesiz...
Article
Full-text available
Ovarian cancer is commonly diagnosed in its late stages, and new treatment modalities are needed to improve patient outcomes and survival. We have recently established the synergistic effects of combination tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and procaspase activating compound (PAC‐1) therapies in granulosa cell tumors (...
Preprint
Full-text available
Virtual clinical trials (VCTs) have gained popularity for their ability to rationalize the drug development process using mathematical and computational modelling, and to provide key insights into the mechanisms regulating patient responses to treatment. In this chapter, we cover approaches for generating virtual cohorts with applications in cancer...
Article
Full-text available
Oncolytic viruses (OVs) are an emerging cancer immunotherapy. Despite notable successes in the treatment of some tumours, OV therapy of central nervous system cancers has failed to show efficacy. We used an ex vivo tumour model developed from human glioblastoma tissue to evaluate the infiltration of herpes simplex OV rQNestin (oHSV-1) into glioblas...
Article
Full-text available
Cyclic thrombocytopenia (CTP) is a rare disease of periodic platelet count oscillations. The pathogenesis of CTP remains elusive. To study the underlying pathophysiology and genetic and cellular associations with CTP, we applied systems biology approaches to two patients with stable platelet cycling and reciprocal thrombopoietin (TPO) cycling at mu...
Article
Full-text available
Data analysis is widely used to generate new insights into human disease mechanisms and provide better treatment methods. In this work, we used the mechanistic models of viral infection to generate synthetic data of influenza and COVID-19 patients. We then developed and validated a supervised machine learning model that can distinguish between the...
Preprint
Ovarian cancer is commonly diagnosed in its late stages, and new treatment modalities are needed to improve patient outcomes and survival. We have recently established the synergistic effects of combination tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and procaspase activating compound (PAC-1) therapies in granulosa cell tumours...
Article
Full-text available
We extend our established agent-based multiscale computational model of infection of lung tissue by SARS-CoV-2 to include pharmacokinetic and pharmacodynamic models of remdesivir. We model remdesivir treatment for COVID-19; however, our methods are general to other viral infections and antiviral therapies. We investigate the effects of drug potency...
Article
Full-text available
Glioblastoma is a complex disease that is difficult to treat. Network and data science offer alternative approaches to classical bioinformatics pipelines to study gene expression patterns from single-cell datasets, helping to distinguish genes associated with the control of differentiation and aggressivity. To identify the key molecular regulators...
Article
Full-text available
The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), has been sequenced at an unprecedented scale leading to a tremendous amount of viral genome sequencing data. To assist in tracing infection pathways and design preventive strategies, a deep understanding of t...
Article
Background: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. Methods: The RAAS-COVID-...
Preprint
Full-text available
Data analysis is widely used to generate new insights into human disease mechanisms and provide better treatment methods. In this work, we used the mechanistic models of viral infection to generate synthetic data of influenza and COVID-19 patients. We then developed and validated a supervised machine learning model that can distinguish between the...
Article
Background: More data is needed on the cardiovascular impact of discontinuing versus continuing renin-angiotensin aldosterone system inhibitors (RAASi) among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). Methods: The McGill RAAS-COVID-19 trial was a randomized, open label trial in adult patients...
Preprint
Full-text available
Background. The lipid nanoparticle (LNP)-formulated mRNA vaccines are a widely adopted two-dose vaccination public health strategy to manage the COVID-19 pandemic. Clinical trial data has described the immunogeneicity of the vaccine, albeit within a limited study time frame. Our aims were to use a within-host mathematical model for LNP-formulated m...
Preprint
Full-text available
Glioblastoma (GBM) is a complex disease that is difficult to treat. Establishing the complex genetic interactions regulating cell fate decisions in GBM can help to shed light on disease aggressivity and improved treatments. Networks and data science offer novel approaches to study gene expression patterns from single-cell datasets, helping to disti...
Article
Full-text available
Purpose of Review Hematopoietic stem cells (HSCs) produce all blood cells via a tightly controlled production system. Disruptions to control mechanisms can induce serious disorders, including leukemias. In this review, we provide an overview of how mathematical modelling has contributed to our understanding of normal and pathological HSC biology....
Article
Full-text available
Intra-tumour heterogeneity is a leading cause of treatment failure and disease progression in cancer. While genetic mutations have long been accepted as a primary mechanism of generating this heterogeneity, the role of phenotypic plasticity is becoming increasingly apparent as a driver of intra-tumour heterogeneity. Consequently, understanding the...
Article
Full-text available
During the SARS-CoV-2 global pandemic, several vaccines, including mRNA and adenovirus vector approaches, have received emergency or full approval. However, supply chain logistics have hampered global vaccine delivery, which is impacting mass vaccination strategies. Recent studies have identified different strategies for vaccine dose administration...
Article
Full-text available
Introduction: To mitigate the risk of neutropenia during chemotherapy treatment of triple-negative breast cancer, prophylactic and supportive therapy with granulocyte colony-stimulating factor (G-CSF) is administered concomitant to chemotherapy. The proper timing of combined chemotherapy and G-CSF is crucial for treatment outcomes. Methods: Leve...
Article
Full-text available
To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly...
Article
Full-text available
Stem cell differentiation cascades are critical components of healthy tissue maintenance. Dysregulation in these systems can lead to serious diseases, including cancer. Myoepithelial mammary cells are produced from differentiated mammary stem cells in processes regulated, in part, by estrogen signalling and concentrations. To quantify and predict t...
Preprint
Full-text available
During the SARS-CoV-2 global pandemic, several vaccines, including mRNA and adenovirus vector approaches, have received emergency or full approval. However, supply chain logistics have hampered global vaccine delivery, which is impacting mass vaccination strategies. Recent studies have identified different strategies for vaccine dose administration...
Article
Full-text available
Granulosa cell tumors (GCT) constitute only ~5% of ovarian neoplasms yet have significant consequences, as up to 80% of women with recurrent GCT will die of the disease. This study investigated the effectiveness of procaspase-activating compound 1 (PAC-1), an activator of procaspase-3, in treating adult GCT (AGCT) in combination with selected apopt...
Article
Full-text available
Objectives The aim of the RAAS-COVID-19 randomized control trial is to evaluate whether an upfront strategy of temporary discontinuation of renin angiotensin aldosterone system (RAAS) inhibition versus continuation of RAAS inhibition among patients admitted with established COVID-19 infection has an impact on short term clinical and biomarker outco...
Article
Full-text available
Background Immunotherapies, driven by immune-mediated antitumorigenicity, offer the potential for significant improvements to the treatment of multiple cancer types. Identifying therapeutic strategies that bolster antitumor immunity while limiting immune suppression is critical to selecting treatment combinations and schedules that offer durable th...
Article
Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clones generate a disproportionate fraction of blood leukocytes, correlates with higher risk for cardiovascular disease. The mechanisms behind this association are incompletely understood. Here, we show that hematopoietic stem cell division rates are increased in mice and...
Preprint
Full-text available
To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results indicate that virtual patients with low production rates of infected cell derived IFN subsequently experienced highl...
Article
Full-text available
Purpose of review: Computational and mathematical modeling have become a critical part of understanding in-host infectious disease dynamics and predicting effective treatments. In this review, we discuss recent findings pertaining to the biological mechanisms underlying infectious diseases, including etiology, pathogenesis, and the cellular intera...
Article
The primary goal of drug developers is to establish efficient and effective therapeutic protocols. Multifactorial pathologies, including dynamical diseases and complex disorders, can be difficult to treat, given the high degree of inter- and intra-patient variability and nonlinear physiological relationships. Quantitative approaches combining mecha...
Article
Drug resistance has profoundly limited the success of cancer treatment, driving relapse, metastasis, and mortality. Nearly all anticancer drugs and even novel immunotherapies, which recalibrate the immune system for tumor recognition and destruction, have succumbed to resistance development. Engineers have emerged across mechanical, physical, chemi...
Article
Full-text available
A central challenge in medicine is translating from observational understanding to mechanistic understanding, where some observations are recognized as causes for the others. This can lead not only to new treatments and understanding, but also to recognition of novel phenotypes. Here, we apply a collection of mathematical techniques (empirical dyna...
Article
Full-text available
In spite of the recent focus on the development of novel targeted drugs to treat cancer, cytotoxic chemotherapy remains the standard treatment for the vast majority of patients. Unfortunately, chemotherapy is associated with high hematopoietic toxicity that may limit its efficacy. We have previously established potential strategies to mitigate chem...
Article
Full-text available
Despite recent advances in immunotherapies, cytotoxic chemotherapy continues to be a first‐line treatment option for the majority of cancers. Unfortunately, a common side effect in patients undergoing chemotherapy treatment is neutropenia. To mitigate the risk of neutropenia and febrile neutropenia, prophylactic treatment with granulocyte‐colony st...
Preprint
Full-text available
The 2019 novel coronavirus, SARS-CoV-2, is an emerging pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known...
Preprint
Full-text available
In spite of the recent focus on the development of novel targeted drugs to treat cancer, cytotoxic chemotherapy remains the standard treatment for the vast majority of patients. Unfortunately, chemotherapy is associated with high hematopoietic toxicity that may limit its efficacy. We have previously established potential strategies to mitigate chem...
Article
Full-text available
Oncolytic virotherapies, including the modified herpes simplex virus talimogene laherparepvec (T-VEC), have shown great promise as potent instigators of anti-tumour immune effects. The OPTiM trial, in particular, demonstrated the superior anti-cancer effects of T-VEC as compared to systemic immunotherapy treatment using exogenous administration of...
Article
Full-text available
Understanding intrinsic and acquired resistance is crucial to overcoming cancer chemotherapy failure. While it is well-established that intratumor, subclonal genetic and phenotypic heterogeneity significantly contribute to resistance, it is not fully understood how tumor sub-clones interact with each other to withstand therapy pressure. Here, we re...
Article
Full-text available
We use the McKendrick equation with variable ageing rate and randomly distributed mat-uration time to derive a state dependent distributed delay differential equation. We show that the resulting delay differential equation preserves non-negativity of initial conditions and we characterise local stability of equilibria. By specifying the distributio...
Preprint
Oncolytic virothcrapics, including the modified herpes simplex virus talimogene laherparepvec (T-VEC), have shown great promise as potent instigators of anti-tumour immune effects. The OPTiM trial in particular demonstrated the superior anti-cancer effects of T-VEC as compared to more traditional immunotherapy treatment using exogenous administrati...
Preprint
Full-text available
Hematopoiesis is a dynamic process involving the up- and down-regulation of genes, as well as feed-back loops that stimulate or suppress circulating cytokine concentrations. More complete pictures of the gene regulatory networks that control the production of the blood system have emerged with the advent of single-cell sequencing techniques and ref...
Preprint
Full-text available
We use the McKendrick equation with variable ageing rate and randomly distributed maturation time to derive a state dependent distributed delay differential equation. We show that the resulting delay differential equation preserves non-negativity of initial conditions and we characterise local stability of equilibria. By specifying the distribution...
Article
In mathematical pharmacology, models are constructed to confer a robust method for optimizing treatment. The predictive capability of pharmacological models depends heavily on the ability to track the system and to accurately determine parameters with reference to the sensitivity in projected outcomes. To closely track chaotic systems, one may choo...
Article
Full-text available
We compare and contrast the transit compartment ordinary differential equation modelling approach with distributed and discrete delay differential equation models. We focus on Quartino's extension to the Friberg transit compartment model of myelosuppression, widely relied upon in the pharmaceutical sciences to predict the neutrophil response after...
Article
Full-text available
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug-polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dol...