Morgan Craig
Profile
Research expertise
Neutrophil and hematopoietic stem cell dynamics
Neutrophils are the most abundant white blood cell in the body and are front-line fighters against bacterial and fungal infections. Neutropenia, or a lack of neutrophils, can have serious implications for people's health, including an inability to ward off infection or life-threatening sepsis. All blood cells are derived from pluripotent hematopoietic stem cells, that self-renew and differentiate to maintain cell counts in the bone marrow and in circulation.
Our approach to study how hematopoiesis/granulopoiesis occurs is to delineate the mechanisms required for the control of hematopoiesis in the body and to use physiology to determine pharmacokinetic and pharmacodynamic relationships and drug models to understand how hematopoiesis normally proceeds and how disruptions/treatments affect the system. Using delay differential equations, we model the hematopoietic system in a physiologically-complete way to study the impact of different endogenous proteins/drugs.
Blood cell production is regulated by a variety of small proteins called cytokines that modulate the total number of cells by controlling the differentiation, proliferation, maturation, and/or the storage of cells in the marrow and circulation. Granulocyte colony-stimulating factor (G-CSF) is the principle cytokine responsible for the regulation of neutrophil counts, and acts in a negative feedback loop with circulating neutrophil numbers to maintain basal concentrations in the blood. During chemotherapy, patients frequently experience neutropenia due to the non-selective cytotoxicity of anti-cancer agents, so exogenous G-CSF is administered to boost cell counts on the system. We study the optimization of exogenous G-CSF treatment with specific reference to the physiological mechanisms of neutrophil production. We are also interested in the rare disease of cyclic neutropenia (and its platelet-analogue cyclic thrombocytopenia), a condition where patients experience continuously oscillating neutrophil (platelet) counts.
My work also combines stochastic approaches to hematopoiesis, specifically with reference to the HSCs, to understand how clones are generated in a variety of normal and pathological conditions.
Reconstructing immune networks
Disordered hematopoietic conditions, like cyclic neutropenia and cyclic thrombocytopenia, give us a window into the multitiude of control networks that regulate the production of blood cells. Using data from individuals with perturbed hematopoieisis and applying dynamical systems and statistical techniques like convergent cross mapping and periodogram analysis, we reconstruct immunological networks of cytokines and blood cells. Clustering and threshold measures allow us to zoom in on the "hubs" that control hematopoiesis to give us a clearer picture of how hematopoiesis is regulated at homeostasis.
PBPK modelling of antiretrovirals to study new drug delivery systems
Though the development of combination antiretroviral (ARV) treatment (highly active antiretrovial therapy, or HAART) has transformed the management of HIV and the prognosis of those living with the infection, several factors account for why ARV treatment cannot be discontinued and why an HIV cure remains elusive. The selection of resistant HIV can be brought about by, for example, imperfect adherence leading to resistant HIV, imperfect drug penetration in HIV sanctuaries or transmission sites, the persistence of latent virus in memory cells.
To study how readily ARV drugs reach crucial sites, and the impact of that penetration on imperfect drug taking patterns, we use physiologically-based pharmacokinetic (PBPK) modelling, which takes into account the many elements affecting the disposition of ARVs in the body. Our hope is that a better understanding of how HIV resistance is impacted by the pharmacokinetics in the whole body will lead to better drug delivery systems and suggestions for HIV cure techniques.
Biography
Adjunct Professor
Department of Physiology
McGill University, Montréal, QC
Postdoctoral Research Fellow, 2016-2018
Organismic and Evolutionary Biology
Harvard University, Cambridge, MA
Université de Montréal, Montréal, QC Canada
Ph.D. (Sciences pharmaceutiques), 2016
Titre : Improving the use of G-CSF during chemotherapy using physiological
mathematical modelling: a quantitative systems pharmacology approach
Directeurs de recherche: Fahima Nekka (Université de Montréal), Michael C Mackey (McGill University)
University of Manitoba, Winnipeg, MB Canada
M.Sc. (Mathematics), 2011
Titre : Incorporating stochastic influences in assembly models: application to intermediate filament polymerisation
Directeur de recherche : Stéphanie Portet (University of Manitoba)
Collège universitaire de Saint-Boniface, Winnipeg, MB Canada
B.Sc. (Mathématiques et Chimie), 2006
Awards and recognitions
- Lee A. Segal Prize for Best Student Paper in the Bulletin of Mathematical Biology, awarded by the Society for Mathematical Biology (2018).
For more information…
- La mathématique analytique en appui aux recherches médicales
- Six projets reçoivent du financement du programme NOVA – FRQNT-CRSNG
- 1,7 milliard pour soutenir la recherche et l’innovation annoncé à l’UdeM
- Les mathématiques aident à la prise de décision dans la lutte contre les maladies infectieuses
- Une «boîte à outils» pour l’aide au diagnostic dans les maladies complexes
Affiliations and responsabilities
Research affiliations
Professional titles and affiliations
Titles: corporations and professional organizations
Teaching and supervision
Teaching
Courses taught (current session only)
Programs
- 119010 – Baccalauréat en mathématiques
- 119020 – Majeure en mathématiques
- 119040 – Mineure en mathématiques
- 119110 – Baccalauréat en mathématiques et informatique
- 119110 – Baccalauréat en mathématiques et informatique
- 119210 – Baccalauréat en mathématiques et physique
- 119210 – Baccalauréat en mathématiques et physique
- 119310 – Baccalauréat en mathématiques et économie
- 119310 – Baccalauréat en mathématiques et économie
- 120010 – Baccalauréat en physique
- 120510 – Baccalauréat en physique et informatique
- 120510 – Baccalauréat en physique et informatique
- 183412 – Baccalauréat en enseignement des mathématiques au secondaire
Student supervision
Theses and dissertation supervision (Papyrus Institutional Repository)
Mathematical modelling of experimental therapy for granulosa cell tumour of the ovary and mammary cell differentiation in the context of triple-negative breast cancer
Cycle : Doctoral
Grade : Ph. D.
L’impact des mutations récurrentes du SARS-CoV-2 sur l’évasion immunitaire
Cycle : Master's
Grade : M. Sc.
Mixed effects modelling for biological systems
Cycle : Master's
Grade : M. Sc.
Optimizing doxorubicin-G-CSF chemotherapy regimens for the treatment of triple-negative breast cancer
Cycle : Master's
Grade : M. Sc.
Projects
Research projects
Modelling cell dynamics and epigenetic changes in 3D spheroids with custom-made hydrogels
Canada Research Chair in Computational Immunology
Centre de recherches mathématiques (CRM)
Démêler l'hétérogénéité de la cinétique et de l'évolution de l'infection par le cytomégalovirus à l'aide de la modélisation mathématique
Démêler l'hétérogénéité de la cinétique et de l'évolution de l'infection par le cytomégalovirus à l'aide de la modélisation mathématique
Modélisation des défis émergents
Centre de recherches mathématiques (CRM)
Dynamiques des réseaux à travers les échelles : illustrer nos relations avec les virus et notre environnement
Characterization of disrupted hematopoiesis by mathematical modelling
Plasmonic optophysiology optogenetics
La médecine quantitative au service de la personnalisation thérapeutique en oncologie
La médecine quantitative au service de la personnalisation thérapeutique en oncologie
One Health Modelling Network for Emerging Infections (OMNI)/RÉseau UNe seule santé sur la modélisation des InfectionS (REUNIS)
Characterization of disrupted hematopoiesis by mathematical modelling
Virtual Patient Cohorts to Illuminate Immunologic Drivers of Influenza Severity. Cohortes de patients virtuels pour prédire la réponse immunitaire à la grippe A
Predicting heterogeneous age-related immune kinetics after COVID-19 vaccination
One Health Modelling Network for Emerging Infections
La médecine quantitative au service de la personnalisation thérapeutique en oncologie
Réseau Québécois de Recherche sur les Médicaments (RQRM) / Integrated quantitative approach to novel targets in triple negative breast cancer.
La médecine quantitative en appui à la personnalisation des thérapies.
Quantitative Approaches to Understand Differential Immune Responses in COVID-19
Supplément COVID-19 CRSNG_Characterization of disrupted hematopoiesis by mathematical modelling
Outreach
Publications and presentations
Publications
Voir Google Scholar
Disciplines
- Applied Mathematics
- Immunology
- Pharmacology
Areas of expertise
- Immune System
- Modelization and Simulation
- Infectious Diseases
- Viral Infections
- Apoptosis and Cancer
- Immunotherapy
- Immune Mediators: Cytokines and Chemokines
- Cell Signaling and Infectious and Immune Diseases
- COVID-19
- AIDS / HIV
- Chemotherapy
- Leukemia
- Cell Signaling and Cancer
- Stem Cells and Organogenesis