Mathematical Modeling

Cancer can arise via multiple pathways. To systematically describe carcinogenesis we aim to design a mathematical framework that can be built in a modular way and that is medically interpretable. In collaboration with mathematicians from EMCL at Heidelberg University and HITS Heidelberg (Saskia Haupt, Alexander Zeilmann, Valentin Schmid, Head: Vincent Heuveline), we model the development of colorectal cancer in Lynch syndrome, the most common hereditary colorectal cancer syndrome, and its consequences on prevention, diagnosis and treatment.

More information about the project can be found under:

https://emcl.iwr.uni-heidelberg.de/research/projects/mathematical-oncology

Engineering Mathematics and Computing Lab (EMCL)

Prof. Dr. Vincent Heuveline, IWR, Heidelberg University

Saskia Haupt, IWR, Heidelberg University

Alexander Zeilmann, IWR, Heidelberg University

Valentin Schmid, IWR, Heidelberg University

https://emcl.iwr.uni-heidelberg.de/research/projects/mathematical-oncology

Møller P, Seppälä T, Dowty JG, Haupt S, Dominguez-Valentin M, Sunde L, Bernstein I, Engel C, Aretz S, Nielsen M, Capella G, Evans DG, Burn J, Holinski-Feder E, Bertario L, Bonanni B, Lindblom A, Levi Z, Macrae F, Winship I, Plazzer JP, Sijmons R, Laghi L, Valle AD, Heinimann K, Half E, Lopez-Koestner F, Alvarez-Valenzuela K, Scott RJ, Katz L, Laish I, Vainer E, Vaccaro CA, Carraro DM, Gluck N, Abu-Freha N, Stakelum A, Kennelly R, Winter D, Rossi BM, Greenblatt M, Bohorquez M, Sheth H, Tibiletti MG, Lino-Silva LS, Horisberger K, Portenkirchner C, Nascimento I, Rossi NT, da Silva LA, Thomas H, Zaránd A, Mecklin JP, Pylvänäinen K, Renkonen-Sinisalo L, Lepisto A, Peltomäki P, Therkildsen C, Lindberg LJ, Thorlacius-Ussing O, von Knebel Doeberitz M, Loeffler M, Rahner N, Steinke-Lange V, Schmiegel W, Vangala D, Perne C, Hüneburg R, de Vargas AF, Latchford A, Gerdes AM, Backman AS, Guillén-Ponce C, Snyder C, Lautrup CK, Amor D, Palmero E, Stoffel E, Duijkers F, Hall MJ, Hampel H, Williams H, Okkels H, Lubiński J, Reece J, Ngeow J, Guillem JG, Arnold J, Wadt K, Monahan K, Senter L, Rasmussen LJ, van Hest LP, Ricciardiello L, Kohonen-Corish MRJ, Ligtenberg MJL, Southey M, Aronson M, Zahary MN, Samadder NJ, Poplawski N, Hoogerbrugge N, Morrison PJ, James P, Lee G, Chen-Shtoyerman R, Ankathil R, Pai R, Ward R, Parry S, Dębniak T, John T, van Overeem Hansen T, Caldés T, Yamaguchi T, Barca-Tierno V, Garre P, Cavestro GM, Weitz J, Redler S, Büttner R, Heuveline V, Hopper JL, Win AK, Lindor N, Gallinger S, Le Marchand L, Newcomb PA, Figueiredo J, Buchanan DD, Thibodeau SN, Ten Broeke SW, Hovig E, Nakken S, Pineda M, Dueñas N, Brunet J, Green K, Lalloo F, Newton K, Crosbie EJ, Mints M, Tjandra D, Neffa F, Esperon P, Kariv R, Rosner G, Pavicic WH, Kalfayan P, Torrezan GT, Bassaneze T, Martin C, Moslein G, Ahadova A, Kloor M, Sampson JR, Jenkins MA; European Hereditary Tumour Group (EHTG) and the International Mismatch Repair Consortium (IMRC).Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium. Hered Cancer Clin Pract. 2022 Oct 1;20(1):36. PMID: 36182917

S. Haupt, N. Gleim, A. Ahadova, H. Bläker, M. Knebel Doeberitz, M. Kloor, V. Heuveline: A computational model for investigating the evolution of colonic crypts during Lynch syndrome carcinogenesis. Computational and Systems Oncology, June 2021.

Haupt S, Zeilmann A, Ahadova A, Bläker H, von Knebel Doeberitz M, Kloor M, Heuveline V. Mathematical modeling of multiple pathways in colorectal carcinogenesis using dynamical systems with Kronecker structure. PLoS Comput Biol. 2021 May 18;17(5):e1008970. PMID: 34003820

Ballhausen A, Przybilla MJ, Jendrusch M, Haupt S, Pfaffendorf E, Seidler F, Witt J, Hernandez Sanchez A, Urban K, Draxlbauer M, Krausert S, Ahadova A, Kalteis MS, Pfuderer PL, Heid D, Stichel D, Gebert J, Bonsack M, Schott S, Bläker H, Seppälä T, Mecklin JP, Ten Broeke S, Nielsen M, Heuveline V, Krzykalla J, Benner A, Riemer AB, von Knebel Doeberitz M, Kloor M.The shared frameshift mutation landscape of microsatellite-unstable cancers suggests immunoediting during tumor evolution. Nat Commun. 2020 Sep 21;11(1):4740. PMID: 32958755 

Bläker H, Haupt S, Morak M, Holinski-Feder E, Arnold A, Horst D, Sieber-Frank J, Seidler F, von Winterfeld M, Alwers E, Chang-Claude J, Brenner H, Roth W, Engel C, Löffler M, Möslein G, Schackert HK, Weitz J, Perne C, Aretz S, Hüneburg R, Schmiegel W, Vangala D, Rahner N, Steinke-Lange V, Heuveline V, von Knebel Doeberitz M, Ahadova A, Hoffmeister M, Kloor M; German Consortium for Familial Intestinal Cancer. Age-dependent performance of BRAF mutation testing in Lynch syndrome diagnostics. Int J Cancer. 2020 Nov 15;147(10):2801-2810. PMID: 32875553 

Involved researchers

Prof. Dr. med. Matthias Kloor
Prof. Dr. med. Matthias Kloor
Dr. Aysel Ahadova
Dr. Aysel Ahadova