Roskilde University Entrance

The Cancitis research group

About Us

Cancitis – an abbreviation of Cancer and the Latin word itis for inflammation - is part of the National Center for Mathematical Modeling - Human Health and Disease (COMMAND) at RUC. The Center for Mathematical Modeling - Health and Disease collaborates with the PandemiX Center, Center for Big Data and Center for Sundhedsfremmeforskning at RUC.

Nationally we have a well established collaboration with Hospitals in Region Copenhagen and in particular Dept. of Hematology, Region Zealand, Roskilde. The collaboration includes co-financed PhD students/postdocs focusing on educating and recruiting young researchers. We are member of the Danish Life Science Cluster “Center for (Early) Diagnosis and Treatment/Clinical Health Data Science” and Key member of the Greater Copenhagen CAG (Clinical Academic Group) initiative “ZIRI: The Zealand Inflammation Research Initiative. Chronic Inflammation, Vascular Diseases, and Cancer. Mutations in Blood Cells - a Common Link?”.

The Cancitis group and the Center for Mathematical Modeling - Health and Disease at RUC host a recent Lundbeck-Foundation’s Fellowship led by Prof. Thomas Stiehl. The Fellowship project on “Mathematical modeling of Acute Leukemia” (2021-2025) is a five-year and 10 Mill DKK grant in collaboration with Zealand University Hospital, Department of Hematology. The team members have successfully been investigating ways to work with Region Zealand and Region Copenhagen blood bank data and the Statens Serum Institute to create a brand new natural observatory for disease protection (antibodies, mutations, etc.) in Danish population age cohorts.

Our Team

Morten Andersen

Associate Professor

RUC Research Profile.

Thomas Stiehl

Associate Professor

Co-appionted at RWTH Aachen University

RUC Research Profile.

Personal Website.

Johanne Gudmand-Høyer

Assistant Professor

RUC Research Profile.

Jordan Andrew Snyder

Assistant Professor

RUC Research Profile.

Personal Website.

Tobias Idor Boklund

Ph.D. student

RUC Research Profile.

Previous members

Marc John Bordier Dam

Ph.D. student

RUC Research Profile.

Rasmus K. Pedersen

Ph.D. graduate, 2020

RUC Research Profile.

Personal Website.

Zamra Sajid

Ph.D. graduate, 2021

RUC Research Profile.

Published articles and other work

2024

Neutrophil-to-lymphocyte ratio and all-cause mortality with and without myeloproliferative neoplasms-a Danish longitudinal study

Published in Blood Cancer Journal

DOI: 10.1038/s41408-024-00994-z

Morten Kranker Larsen, Vibe Skov, Lasse Kjær, Christina Schjellerup Eickhardt-Dalbøge, Trine Alma Knudsen, Marie Hvelplund Kristiansen, Anders Lindholm Sørensen, Troels Wienecke, Morten Andersen, Johnny T. Ottesen, Johanne Gudmand-Høyer, Jordan Andrew Snyder, Mikkel Porsborg Andersen, Christian Torp-Pedersen, Henrik Enghusen Poulsen, Thomas Stiehl, Hans Carl Hasselbalch, Christina Ellervik

Link to journal

Mathematical modelling of stem and progenitor cell dynamics during ruxolitinib treatment of patients with myeloproliferative neoplasms

Published in Frontiers in Immunology, Sec. Cancer Immunity and Immunotherapy

DOI: 10.3389/fimmu.2024.1384509

Tobias Idor Boklund, Jordan Snyder, Johanne Gudmand-Hoeyer, Morten Kranker Larsen, Trine Alma Knudsen, Christina Schjellerup Eickhardt-Dalbøge, Vibe Skov, Lasse Kjær, Hans C. Hasselbalch, Morten Andersen, Johnny T. Ottesen and Thomas Stiehl

Link to journal

2023

Aging, Inflammation, and Comorbidity in Cancers—A General In Silico Study Exemplified by Myeloproliferative Malignancies

Published in Cancers, Special Issue on Mechanisms and Models of Comorbidities in Cancer Progression and Treatments

DOI: 10.3390/cancers15194806

Johnny T. Ottesen and Morten Andersen

Link to journal

Therapeutic cancer vaccination against mutant calreticulin in myeloproliferative neoplasms induces expansion of specific T cells in the periphery but specific T cells fail to enrich in the bone marrow

Published in Frontiers in Immunology, 2023; 14: 1240678.

DOI: 10.3389/fimmu.2023.1240678

Morten Orebo Holmström, Morten Andersen, Sofie Traynor, Shamaila Munir Ahmad, Thomas Landkildehus Lisle, Jacob Handlos Grauslund, Vibe Skov, Lasse Kjær, Johnny T. Ottesen, Morten Frier Gjerstorff, Hans Carl Hasselbalch, and Mads Hald Andersen

Link to journal

How do cell crowding and starvation affect avascular tumor growth of the EMT6/Ro tumor?

Published in Math. Model. Nat. Phenom. 18 (2023) 8

DOI: 10.1051/mmnp/2023007

Bjarke Spangsberg Bak, Morten Andersen, Johnny T. Ottesen and J.S. Hansen

Link to journal

Case Report: First longitudinal study of a patient with CALR positive clonal hematopoiesis of indeterminate potential developing into pre-fibrotic myelofibrosis

Published in Frontiers in Oncology, 2023; 13: 1176173.

DOI: 10.3389/fonc.2023.1176173

Lasse Kjær, Vibe Skov, Morten Kranker Larsen, Tobias Idor Boklund, Morten Andersen, Maria Kefala, Trine A. Knudsen, Christina Schjellerup Eickhardt-Dalbøge, Thomas Stiehl, Johanne Gudmand-Høyer, Jordan Snyder, Morten Holmström, Mads H. Andersen, Johnny T. Ottesen, Christina Ellervik, and Hans C. Hasselbalch

Link to journal

A novel integrated biomarker index for the assessment of hematological responses in MPNs during treatment with hydroxyurea and interferon-alpha2

Published in Cancer Medicine, 2023, 12(4), 4218-4226.

DOI: 10.1002/cam4.5285

Marc J. B. Dam, Rasmus K. Pedersen, Trine A. Knudsen, Morten Andersen, Christina Ellervik, Morten Kranker Larsen, Lasse Kjær, Vibe Skov, Hans C. Hasselbalch, and Johnny T. Ottesen

Link to journal

Understanding Hematopoietic Stem Cell Dynamics—Insights from Mathematical Modelling

Published in Current Stem Cell Reports volume 9, pages 9-16 (2023)

DOI: 10.1007/s40778-023-00224-5

Rasmus K. Pedersen, Morten Andersen, Thomas Stiehl, and Johnny T. Ottesen

Link to journal

HSC Niche Dynamics in Regeneration, Pre-malignancy, and Cancer: Insights From Mathematical Modeling

Published in Stem Cells, Volume 41, Issue 3, March 2023, Pages 260-270

DOI: 10.1093/stmcls/sxac079

Rasmus Kristoffer Pedersen, Morten Andersen, Vibe Skov, Lasse Kjær, Hans C Hasselbalch, Johnny T Ottesen, and Thomas Stiehl

Link to journal

2022

Clonal haematopoiesis of indeterminate potential and impaired kidney function—A Danish general population study with 11 years follow-up

Published in European Journal of Haematology (2022)

DOI: 10.1111/ejh.13845

Morten K. Larsen, Vibe Skov, Lasse Kjær, Natascha A. Møller-Palacino, Rasmus K. Pedersen, Morten Andersen, Johnny T. Ottesen, Sabrina Cordua, Henrik E. Poulsen, Morten Dahl, Trine A. Knudsen, Christina Schjellerup Eickhardt-Dalbøge, Steffen Koschmieder, Kasper M. Pedersen, Yunus Çolak, Stig E. Bojesen, Børge G. Nordestgaard, Thomas Stiehl, Hans C. Hasselbalch, Christina Ellervik

Link to journal

Neutrophil-to-Lymphocyte Ratio As a Predictor of All-Cause Mortality in the General Population and Patients with Myeloproliferative Neoplasms

Poster presented at the 64th annual meeting of the American Society of Hematology

DOI: 10.1182/blood-2022-165252

Morten Kranker Kranker Larsen, Vibe Skov, Lasse Kjær, Henrik E. Poulsen, Christina S. Eickhardt-Dalbøge, Trine A. Knudsen, Sarah F. Christensen, Anders L. Sørensen, Marie H. Kristiansen, Troels Wienecke, Rasmus K. Pedersen, Morten Andersen, Johnny T. Ottesen, Thomas Stiehl, Christina Ellervik, and Hans Carl Hasselbalch

Link to journal

2021

Potential of Immunotherapies in Treating Hematological Cancer-Infection Comorbidities—A Mathematical Modelling Approach

Published in Cancers (Basel). 2021 Aug; 13(15): 3789.

DOI: 10.3390/cancers13153789

Johnny T. Ottesen and Morten Andersen

Link to journal

Data-driven analysis of the kinetics of the JAK2V617F allele burden and blood cell counts during hydroxyurea treatment of patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis

Published in European Journal of Haematology (2021); 107:624-633.

DOI: 10.1111/ejh.13700

Marc J. B. Dam, Rasmus K. Pedersen, Trine A. Knudsen, Morten Andersen, Vibe Skov, Lasse Kjær, Hans C. Hasselbalch, and Johnny T. Ottesen

Link to journal

System dynamics of cancer in erythropoiesis with multiple EPO feedbacks

Published in System Dynamics Review, 2021, 36(4)

DOI: 10.1002/sdr.1670

Zamra Sajid, Morten Andersen and Johnny T. Ottesen

Link to journal

Mathematical modelling of the hematopoietic stem cell-niche system: Clonal dominance based on stem cell fitness

Published in Journal of Theoretical Biology, 2021, 518

DOI: 10.1016/j.jtbi.2021.110620

Rasmus Kristoffer Pedersen, Morten Andersen, Thomas Stiehl and Johnny T. Ottesen

Link to journal

Blood Cancer and Immune Surveillance

Published in Systems Medicine: Integrative, Qualitative and Computational Approaches; Volume 3, 2021, Pages 261-268

DOI: 10.1016/B978-0-12-801238-3.11510-7

Johnny T. Ottesen, Thomas Stiehl, and Morten Andersen

Link to journal

2020

Dynamics of competing heterogeneous clones in blood cancers explains multiple observations - a mathematical modeling approach

Published in Mathematical Biosciences and Engineering, 2020, 17(6)

DOI: 10.3934/mbe.2020389

Katrine O. Bangsgaard, Morten Andersen, Vibe Skov, Lasse Kjær, Hans C. Hasselbalch and Johnny T. Ottesen

Link to journal View PDF

Global dynamics of healthy and cancer cells competing in the hematopoietic system

Published in Mathematical Biosciences, 2020, 326

DOI: 10.1016/j.mbs.2020.108372

Morten Andersen, Hans C. Hasselbalch, Lasse Kjær, Vibe Skov and Johnny T. Ottesen

Link to journal View PDF

Data-driven analysis of JAK2V617F kinetics during interferonalpha2 treatment of patients with polycythemia vera and related neoplasms

Published in Cancer Medicine, January 2020

DOI: 10.1002/cam4.2741

Rasmus K. Pedersen, Morten Andersen, Trine A. Knudsen, Zamra Sajid, Johanne Gudmand-Hoeyer, Marc J. B. Dam, Vibe Skov, Lasse Kjær, Christina Ellervik, Thomas S. Larsen, Dennis Hansen, Niels Pallisgaard, Hans C. Hasselbalch and Johnny T. Ottesen

Link to journal View PDF View supplementary material

2019

Mathematical Analysis of the Cancitis model and the role of inflammation in blood cancer progression.

Published in Mathematical Biosciences and Engineering, 2019, 16(6)

DOI: 10.3934/mbe.2019418

Zamra Sajid, Morten Andersen and Johnny T. Ottesen

Link to journal View PDF

Bridging blood cancers and inflammation: The reduced Cancitis model

Published in Journal of Theoretical Biology, 2019, Volume 465

DOI: 10.1016/j.jtbi.2019.01.001

Johnny T. Ottesen, Rasmus K. Pedersen, Zamra Sajid, Johanne Gudmand-Høyer, Katrine O. Bangsgaard, Vibe Skov, Lasse Kjær, Trine A. Knudsen, Niels Pallisgaard, Hans C. Hasselbalch, and Morten Andersen

Link to journal View PDF Additional info and figures

Superiority of IFN Versus HU Using a Novel Biomarker-Based Tool for Assessment of Disease Burden in MPNs

Poster presented at the 61st annual meeting of the American Society of Hematology

DOI: 10.1182/blood-2019-126819

Vibe Skov, Marc JB Dam, Rasmus K Pedersen, Morten Andersen, Trine Alma Knudsen, Zamra Sajid, Lasse Kjær PhD, Christina Ellervik, Hans Hasselbalch, and Johnny T Ottesen

Link to journal

2017

Mathematical Modelling as a Proof of Concept for MPNs as a Human Inflammation Model for Cancer Development

Published in PLoS One, 2017 12(8)

DOI: 10.1371/journal.pone.0183620

Morten Andersen, Zamra Sajid, Rasmus K. Pedersen, Johanne Gudmand-Hoeyer, Christina Ellervik, Vibe Skov, Lasse Kjær, Niels Pallisgaard, Torben A. Kruse, Mads Thomassen, Jesper Troelsen, Hans Carl Hasselbalch, Johnny T. Ottesen

Link to journal View PDF View supplementary material

Collaborators

Members of the Cancitis group at RUC together with some of our Zealand University Hospital collaborators in November 2022. From left to right: Vibe Skov, Tobias Idor Boklund, Johanne Gudmand-Høyer, Johnny T. Ottesen, Hans C. Hasselbalch, Morten Kranker Larsen, Trine A. Knudsen, Morten Andersen, Thomas Stiehl, and Jordan Snyder.
  • Hans Hasselbalch, Lasse Kjær, Vibe Skov, Trine A. Knudsen, Christina Schjellerup Eickhardt-Dalbøge, and Morten K. Larsen
    Hematological Department, Zealand University Hospital, Denmark
  • Thomas Stiehl and Steffen Koschmieder
    Aachen University Medical Center, Germany
  • Mads Hall Andersen
    National Center for Cancer Immune therapy (CCIT-dk), University Hospital Herlev, Denmark
  • Lars Rønn Olesen
    Cancer Genomics, Section for Bioinformatics, DTU Health Technology & Center for Genomic Medicine, Copenhagen University Hospital
  • Claus Henrik Nielsen
    Rigshospitalet
  • Nina Øbro
    Dept of Clinical Immunology Copenhagen University Hospital, Rigshospitalet
  • Helen Byrne
    Applied Mathematics, Mathematical Institute University of Oxford
  • David Kent
    Department of Biology, York University, UK
  • Ann Mullally
    Department of Medicine Harvard University
  • Christina Ellervik
    Harvard Medical School, Boston, USA
  • Mette Olufsen
    Bio-mathematics, NCSU, USA
  • Aurelius de los Reyes V
    University of the Philippines, Philippines

Other things

Presentations, posters and seminars.

"Modelling Hematopoietic Stem Cells and their Interaction with the Bone Marrow Microenvironment"

Talk (Online) - Statistic and Biomathematics Seminar, Chalmers University of Technology, Gothenburg - April 21st 2020

Rasmus Kristoffer Pedersen

Slides

Stem Cell Modelling Day

Seminar at Roskilde University - September 18th 2019

Speakers: Rasmus Kristoffer Pedersen (Roskilde University), Thomas Stiehl (Heidelberg University), Jesper Troelsen (Roskilde University) and Peter Ashcroft (ETH Zurich)

"Hematopoiesis or inflammation driven blood cancer? Insights from mathematical modelling"

Talk - SMB 2019, Montreal

Morten Andersen

"Modelling Myeloproliferative Neoplasms - Dynamics of myeloid cell lin for Ph-negative MPNs"

Poster - SMB 2019, Montreal

Zamra Sajid

"Modelling the Dynamics of Hematopoietic Stem Cells"

Poster - SMB 2019, Montreal

Rasmus Kristoffer Pedersen

"The Cancitis model: a coupled leukemic-inflammatory response"

Talk - ECMTB 2018, Lisbon

Johnny T. Ottesen

"Mathematical modelling of blood cancer evolution"

Talk - ECMTB 2018, Lisbon

Morten Andersen

"Modelling the myeproliferative neoplasms (MPNs): Stability analysis & sensitivty analysis"

Poster - ECMTB 2018, Lisbon

Zamra Sajid

"Modelling of quiescent stem cells in relation to myeloproliferative neoplasms"

Poster - ECMTB 2018, Lisbon

Rasmus Kristoffer Pedersen

Outreach and dissemination

Hematologic Biomarker Index

Animation of the Hematologic Biomarker Index

Cohort of patients treated with either Hydroxyurea or Interferon-alpha animated over time from baseline (time of diagnoses) to 36 month after. First axis show percent changes in JAK2 allele burden and second axis shows the hematopoietic Biomarker Index (HBI), a weighted average of distance to normalized blood cell levels. Full remission corresponds to be at the lower left corner of the diagram. To calculate the HBI we determine the distance from the normal level for each of the three biomarkers (leucocyte count, platelet count and LDH). If a measurement lies above the normal level we calculate the distance to the upper limit of the normal level and if the measurement lies below the normal level we calculate the distance to the lower limit of the normal level. If a measurement falls within the normal level it adds zero to the HBI. To give each biomarker comparable weight we weigh the distances by the upper limit for the normal level of each biomarker. An example of the HBI calculation: The numbers indicate how far from the normal level each measurement is. The measurements which fall inside the normal levels do not contribute to the HBI. Taking the final measurement as an example the thrombocyte contribution is 264/390 ≈ 0.68, the leucocyte contribution is 4.0/8.8 ≈ 0.45 and the LDH contribution is 123/230 ≈ 0.53 and thus the HBI in this case is approximately 0.68 + 0.45 + 0.53 = 1.66. If the three cell counts were all in the normal range the HBI would be 0.

"SRP/SOP materiale"

High-school teaching material

Problem-statements and examples for use for danish high-school students working on either SRP or SOP assignments.

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"Gryende forskningsfelt: Matematikere og læger er et godt mathc"

"Ugeskriftet for Læger" article

Danish article about our collaboration with clinicians.

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"Matematik giver mere effektiv kræftbehandling"

"Tæt på Videnskaben" article

Danish article about blood cancers and our work.

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"Undervisningspakke - Matematisk modellering af cancer"

High-school teaching material (Only in danish)

Collection of various material, intended for use in danish high-school in collaboration with Roskilde University.

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Video (In danish)

"Så Vidt Vi Ved - P1"

Radio-interview (Only in danish)

Danish radio feature about mathematical modelling and blood cancers.

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Student projects

"Forudsigelser og beregninger i evolutionær spilteori og anvendelsen af dem i forbindelse med modellering af cancer"

Student project

2020

Malthe Frøkjær-Rubbås

"Investigating the Structural Identifiability Analysis by Extended Observability Method"

Bachelor Thesis and Subject Module

2019

Magnus Skjold Frederiksen, Uffe Bundesen, Karl Skovfoged Nordentoft, Kenny Haslund Andersen, Max Thrane Nielsen and Poul Thrane

"Modeling the interaction between the immune system and leukemia"

Bachelor 1st semester project

2019

Stine G. Fohrmann, Lukas Rasocha, Jūlija Tumanovska, Julien Hirsch and Kata M. Riegels

"Matematisk modellering af dynamikken mellem T-celler og cancerceller"

Bachelor 2nd semester project

2019

Ilayda Dilara Pusat, Emira Havkic and Kimmie Britoft

"Bag om Matematisk Modellering"

Bachelor 3rd semester project

2018

Bjørn Dan Orfang Nielsen, Frederik Vedel Gantzel, Karl Skovfoged Nordentoft, Kenny Haslund Andersen, Max Thrane Nielsen and Poul Thrane

"Matematisk modellering af non-hodgkins lymfoma"

Bachelor semester project

2018

Daniel Vestma Norén, Emely Overby, Kimmie Schäfferling Britoft, Mads Jens Køie Nielsen, Mette Michelle Unterborg Alempiew and Michelle Vigant Nielsen

"Mathematical Modeling of Blood Cancer"

Master semester project

2018

Katrine O. Bangsgaard

"How can a mathematical model aid in curing leukaemia?"

Bachelor semester project

2018

Mathis Brette Mortensen, Natalia Stati, Irida Gkouzou and Magnus Skjold Frederiksen

"Parameters estimation in a Myeloproliferative Neoplasm model"

Master semester project

2017

Jeannie Bøg Rasmussen, Maria Nørr and Mehmet Temizsoy

"Quasi-SteadyState assumption on a Mathematical Model of Leukemia"

Bachelor semester project

2017

Mikkel Zielinski Ajslev, Hasan M. M. Osman and Stefan Bisgaard

The Cancitis Model

Our main work concerns the Cancitis Model, as introduced in our 2017 PLOS One paper. Below is a schematic overview of the compartments of the model.

The corresponding system of ordinary differential equations is given as:

$$ \begin{align} \frac{dx_0}{dt} &= (r_x \phi_x s- a_x - d_{x0}) x_0 - r_m s x_0 \\ \frac{dx_1}{dt} &= a_x A_x x_0 - d_{x1} x_1 \\ \frac{dy_0}{dt} &= (r_y \phi_y - a_y - d_{y0}) y_0 + r_m s x_0 \\ \frac{dy_1}{dt} &= a_y A_y y_0 - d_{y1} y_1 \\ \frac{da}{dt} &= d_{x0} x_0 + d_{y0} y_0 + d_{x1} x_1 + d_{y1} y_1 -e_a a s\\ \frac{ds}{dt} &= r_s a - e_s s + I \end{align} $$
where \( \phi_x (x_0,y_0) = \frac{1}{1+c_{xx}x_0 + c_{xy}y_0} \) and \( \phi_y (x_0,y_0) = \frac{1}{1+c_{yx}x_0 + c_{yy}y_0} \)

In our 2019 JTB paper (Ottesen et al, 2019), we showed that a model reduction is possible. More information and additional figures can be found here.