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Natural Sciences and Engineering; Medical Sciences; Applied Sciences

Morgan Craig

Professeure adjointe

Faculté des arts et des sciences - Département de mathématiques et de statistique

André-Aisenstadt, room 5243

morgan.craig@umontreal.ca

Secondary number: 514 343-7471 (Travail 1)

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).

Affiliations and responsabilities

Professional titles and affiliations

Titles: corporations and professional organizations

Teaching and supervision

Student supervision

Theses and dissertation supervision (Papyrus Institutional Repository)

2021

Optimizing doxorubicin-G-CSF chemotherapy regimens for the treatment of triple-negative breast cancer

Graduate : Paredes Bonilla, Rosalba Vivian
Cycle : Master's
Grade : M. Sc.

Projects

Research projects

2022 - 2029

Centre de recherches mathématiques (CRM)

Lead researcher : Octavian Cornea
Co-researchers : Yoshua Bengio , François Lalonde , Gilles Brassard , Michel Delfour , Marlène Frigon , Véronique Hussin , Christiane Rousseau , Jacques Bélair , Paul M Gauthier , Sabin Lessard , Alain Vinet , Nadia El-Mabrouk , Gena Hahn , Christian Léger , Fahima Nekka , Iosif Polterovich , Yvan Saint Aubin , Andrew Granville , Sylvie Hamel , Manuel Morales , François Perron , Mylène Bédard , Pierre Duchesne , Matilde Lalin , Robert Gwyn Owens , Manu Paranjape , Dana Schlomiuk , Luc Vinet , Hugo Chapdelaine , Mireille Schnitzer , Karim Jerbi , Alexander Fribergh , Alejandro Murua , Maciej Augustyniak , Benoît Mâsse , Dimitrios Koukoulopoulos , Jun Li , Benjamin Seamone , William Witczak-Krempa , Egor Shelukhin , Morgan Craig , Guillaume Lajoie , Margarida Carvalho , Guy Wolf , Florian Maire , Frédéric Dupont-Dupuis , Michael C. Mackey , Frédéric Lesage , Russell Steele , Erica Moodie , Paul François , Henri Darmon , Maxime Descoteaux , Prakash Panangaden , André Dieter Bandrauk , Peter Bartello , Chantal David , Jean-Marc Lina , R Platt , Anthony Raymond Humphries , John P. Harnad , Jacques Claude Hurtubise , Pengfei Guan , John A Toth , Niky Kamran , Adrian Iovita , Eyal Goren , Dmitry Jakobson , Vojkan Jaksic , Daniel Tzvi Wise , André Garon , Éric P. Marchand , Debbie Janice Dupuis , Yogendra Chaubey , Pawel Gora , Hershy Kisilevsky , Galia Dafni , D. Korotkin , Marco Bertola , Alina Stancu , Lea Popovic , Ibrahim Assem , Tomasz Kaczynski , Shiping Liu , Vasilisa Shramchenko , Bruno L. Rémillard , Richard Fournier , Alfred Michel Grundland , David Stephens , Xiaowen Chang , Frederic Guichard , Erik P. Cook , Robert Brandenberger , Adrian Vetta , Keshav Dasgupta , Christophe Grova , Gantumur Tsogtgerel , Johanna Neslehova , Jean-Christophe Nave , Anmar Khadra , Adam M. Oberman , Michael Yves Michel Pichot , Alexander Maloney , Dana Louigi Addario-Berry , José Garrido , Alexei Kokotov , Wei Sun , Patrice Gaillardetz , Linan Chen , Piotr Przytycki , Vladimir Makarenkov , Louis-Paul Rivest , François Bergeron , Steven P. Boyer , Line Baribeau , Frédéric Gourdeau , Claude Levesque , Thomas Joseph Ransford , Jean-Marie De Koninck , Javad Mashreghi , Thierry Duchesne , Srecko Brlek , Christophe Reutenauer , Vestislav Apostolov , Steven Lu , Geneviève Lefebvre , Hélène Cossette , Étienne Marceau , José Manuel Urquiza , Michael Lau , Alexandre Girouard , Antonio Lei , Jean-François Renaud , Christophe Hohlweg , Mathieu Boudreault , FRANCO SALIOLA , Alexandre Roch , Frédéric Rochon , Alexandre Blondin-Massé , Clement Hyvrier , Denis Talbot , Alexandre Bureau , Fabrice Larribe , Aurélie Labbe , Cody Hyndman , Khader Khadraoui , Hamed Hatami , Roger Villemaire , Frédéric Godin , Marcin Sabok , Yi Yang , Anne Mackay , Jérôme Vétois , Ting-Huei Chen , Habib Benali , Taoufik Bouezmani , Christian Genest , Xiaowen Zhou , Sorana Froda , Mélina Mailhot , Alexandra Schmidt , Simon Philippe Caron-Huot , Abdoulaye Banire Diallo , Jean-Philippe Lessard , Sarah Harrison , Anne-Sophie Charest , Masoud Asgharian-Dastenael , Rustum Choksi , Abbas Khalili Mahmoudabadi , Simon Gravel , Arusharka Sen , Arthur Charpentier , Mathieu Pigeon , Benoit Larose , Thomas Brüstle , Laurent Charlin , Janosch Ortmann , Tim Hoheisel , Jean Deteix , Jessica Lin , Michael Lipnowski , Giovanni Rosso , Thomas Hugh , Jean-Philippe Burelle , Julien Keller , Félix Camirand Lemyre , Marie-Pier Côté , Damir Kinzebulatov , Duncan McCoy , Klaus Herrmann , Felix Kwok , Courtney Paquette , Anush Tserunyan , Suresh Krishna , Valentino Tosatti , Patrick Brodie Allen
Funding sources: FRQNT/Fonds de recherche du Québec - Nature et technologies (FQRNT)
Grant programs: PVXXXXXX-(RS) Programme de regroupements stratégiques
2022 - 2027

Centre de recherches mathématiques (CRM)

Lead researcher : Octavian Cornea
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-(DIS) Appui à la découverte dans les instituts de recherche
2022 - 2025

Plasmonic optophysiology optogenetics

Funding sources: SPIIE/Secrétariat des programmes interorganismes à l’intention des établissements
Grant programs: PVXXXXXX-Fonds Nouvelles frontières en recherche - Exploration
2021 - 2025

La médecine quantitative au service de la personnalisation thérapeutique en oncologie

Lead researcher : Morgan Craig
Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Établissement de jeunes chercheurs Juniors 1
2021 - 2025

La médecine quantitative au service de la personnalisation thérapeutique en oncologie

Lead researcher : Morgan Craig
Funding sources: FRQS/Fonds de recherche du Québec - Santé (FRSQ)
Grant programs: PVXXXXXX-Bourse de chercheur-boursier : Junior 1
2018 - 2025

Characterization of disrupted hematopoiesis by mathematical modelling

Lead researcher : Morgan Craig
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVX20965-(RGP) Programme de subvention à la découverte individuelle ou de groupe
2018 - 2024

Characterization of disrupted hematopoiesis by mathematical modelling

Lead researcher : Morgan Craig
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-(DGECR) Tremplin vers la découverte
2021 - 2023

One Health Modelling Network for Emerging Infections (OMNI)/RÉseau UNe seule santé sur la modélisation des InfectionS (REUNIS)

Lead researcher : Huaiping Zhu
Co-researchers : Morgan Craig
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-Initiative de modélisation des maladies infectieuses émergentes
2021 - 2023

One Health Modelling Network for Emerging Infections

Co-researchers : Morgan Craig , Simon de Montigny
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-Initiative de modélisation des maladies infectieuses émergentes
2020 - 2022

La médecine quantitative en appui à la personnalisation des thérapies.

Lead researcher : Morgan Craig
Funding sources: Fondation de l'Hôpital Ste-Justine
Grant programs:
2020 - 2021

Supplément COVID-19 CRSNG_Characterization of disrupted hematopoiesis by mathematical modelling

Lead researcher : Morgan Craig
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-Supplément à l’appui des étudiants, des stagiaires postdoctoraux et du personnel de soutien à la recherche COVID-19
2020 - 2021

Quantitative Approaches to Understand Differential Immune Responses in COVID-19

Lead researcher : Morgan Craig
Co-researchers : Julie Hussin
Funding sources: CRSNG/Conseil de recherches en sciences naturelles et génie du Canada (CRSNG)
Grant programs: PVXXXXXX-Subventions Alliance

Outreach

Publications and presentations

Publications

1. T. CassidyM. Craig. Determinants of combination GM-CSF immunotherapy and oncolytic virotherapy success identified through in silico treatment personalization. Submitted to: PLOS Computational Biology, Special Issue on Targeted Anticancer Therapies and Precision Medicine in Cancer. 2019 (in print).

2. M. Craig, K. Kaveh, S. Chen, E. Eton, A. Dhawan, D. Goldman, A. Kazuya, M. Rahman, M.A. Nowak, A. Goldman. Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous tumors.  PLOS Computational Biology 15(8):e1007278. 2019. Journal cover (August 2019).

3. T. CassidyM. Craig, A.R. Humphries (2019). Equivalences between age structured models and state dependent distributed delay differential equations. Mathematical Biosciences and Engineering16(5):5419-5450. 2019.

4. N. Pillai, M. Craig, A. Dokoumetzidis, S.L. Schwartz, R. Bies, I. Freedman. Chaos synchronization and Nelder-Mead search for parameter estimation in nonlinear pharmacological systems: Estimating tumor antigenicity in a model of immunotherapy. Progress in Biophysics and Molecular Biology, 139:29-30. 2018. 

5. A.R. Kirtane, O. Abouzid, D. Minaham, T. Bensel, A.L. Hill, C. Selinger, A. Bershteyn, S.S. Mo, M. Craig, H. Mazdiyasni, C. Cleveland, J. Rogner, Y-A. Lee, L. Booth, F. Javid, T. Grant, A.M. Bellinger, B. Nikolic, A. Hayward, L. Wood, P.A. Eckhoff, M. A. Nowak, R. Langer, and G. Traverso. Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy. Nature Communications9(1):pp. 12. 2018. 

6. Transit and lifespan in neutrophil production: implications for drug intervention. Journal of Pharmacokinetics and Pharmacodynamics45(1):59-77. 2018. [*=Co-first authors] 

7. G.P. Langlois, M Craig, A.R. Humphries, M.C. Mackey, J.M. Mahaffy, J. Bélair, T. Moulin, S.R. Sinclair, and L. Wang. 2017. Normal and pathological dynamics of platelets in humans. Journal of Mathematical Biology75(6-7):1141-1462. 2018. 

8. M. Craig. Towards quantitative systems pharmacology models of chemotherapy-induced neutropenia. CPT: Pharmacometrics & Systems Pharmacology6(5):293-304. 2017.

9. M. Craig, A.R. Humphries, and M.C. Mackey. An upper bound for the half-removal time of neutrophils from the blood. Blood128(15):1989-1991. 2016. 

10. M. Craig, M. González-Sales, J. Li, and F. Nekka. Approaching pharmacometrics as a paleontologist would: Recovering the links between drugs and the body through reconstruction. CPT: Pharmacometrics & Systems Pharmacology5(3):158-160. 2016. 

11. M. Craig, A.R. Humphries, and M.C. Mackey. A Mathematical model of granulopoiesis incorporating the negative feedback dynamics and kinetics of G-CSF/neutrophil binding and internalization. Bulletin of Mathematical Biology78(12):2304-2357. 2016. 

12. M. Craig, M. González-Sales, J. Li, and F. Nekka. Impact of pharmacokinetic variability on a mechanistic physiological pharmacokinetic/pharmacodynamic model: a case study of neutrophil development, PM00104, and filgrastim. In Mathematical Sciences with Multidisciplinary Applications, edited by B. Toni, p. 91-112. New York: Springer Science + Business Media. 2016. 

13. M. Craig, A.R. Humphries, F. Nekka, J. Bélair, J. Li, and M.C. Mackey. Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: mathematical modelling guides dose optimisation to minimise neutropenia. Journal of Theoretical Biology385:77-89. 2015. 

Disciplines

  • Applied Mathematics
  • Physiology
  • Pharmacy

Areas of expertise

  • Modelization and Simulation
  • Immune Mediators: Cytokines and Chemokines
  • Leukocytes
  • Stem Cells and Organogenesis
  • Pathology
  • Immune System
  • Platelets
  • Differential Equation
  • Cell Signaling (Circulatory and Respiratory Health)
  • Cell Signaling and Infectious and Immune Diseases
  • AIDS / HIV
  • Antivirals
  • Chemotherapy
  • Immunotherapy
  • Apoptosis and Cancer
  • Leukemia
  • Viral Infections
  • Bacterial Infections
  • Drug Metabolism
  • Infectious Diseases
  • Physiology
  • Cell Signaling and Cancer
  • COVID-19
  • COVID19