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Dominik Wodarz

Research

Mathematical and Computational Models of Biological Processes

My lab works on mathematical and computational models of biomedical processes and diseases, based on ecological and evolutionary principles. We view the in vivo environment as an ecosystem in which different types of cells interact and evolve over time. The models are rooted in population dynamics and evolutionary dynamics, and provide insights into both the process of disease development and treatments. An example is our work on cancer dynamics, in which tissue and tumor cells are modeled as evolving populations in the context of complex ecological interactions within their microenvironment, involving processes such as competition or cooperation. Another example is our work on the in vivo dynamics of viruses and the immune system, which are again driven by a variety of ecological and evolutionary processes. This cross-disciplinary view of disease dynamics can yield a better understanding of disease biology and the correlates of treatment outcomes that are valuable from a biomedical and clinical point of view. It can further provide interpretations of experimental and clinical data that would otherwise seem counter-intuitive. Through close collaborations with experimental and clinical laboratories, our mathematical and computational models are applied to data to estimate parameters, interpret observations, make testable predictions, guide future experiments to test models, and make clinically translatable predictions about therapy outcomes. The synergy between theoretical models and experimental/clinical data is a cornerstone of this work.

Our research typically falls within the following three categories:

  • Evolutionary theory, evolutionary dynamics, and population dynamics
  • Mathematical oncology: carcinogenesis, cancer evolution, and cancer therapy
  • Dynamics of virus infections and the immune system

Select Publications

  • Wodarz D and Komarova NK (2023) Mutant fixation in the presence of a natural enemy. Nature Communications 14, 6642
  • Patel AG, Chen X, Huang X, Clay MR, Komarova N, Krasin MJ, Pappo A, Tillman H, Orr BA, McEvoy J, Gordon B, Blankenship K, Reilly C, Zhou X, Norrie JL, Karlstrom A, Yu J, Wodarz D, Stewart E, Dyer MA (2022). The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma. Developmental Cell 57(10):1226-40.
  • Uhl P, Lowengrub J, Komarova NL & Wodarz D (2022) Spatial dynamics of feedback and feedforward regulation in cell lineages. PLOS Computational Biology, 18(5):e1010039.
  • Wang Y, Boland CR, Goel A, Wodarz D, & Komarova NL (2022) Aspirin’s effect on kinetic parameters of cells contributes to its role in reducing incidence of advanced colorectal adenomas, shown by a multiscale computational study. Elife, 11, p.e71953.
  • Kim JT, Zhang TH, Carmona C, Lee B, Seet CS, Kostelny M, Shah N, Chen H, Farrell K, Soliman MSA, Dimapasoc M, Sinani M, Blanco KYR, Bojorquez D, Jiang H, Shi Y, Du Y, Komarova NL, Wodarz D, Wender PA, Marsden MD, Sun R, Zack JA (2022) Latency reversal plus natural killer cells diminish HIV reservoir in vivo. Nature Communications. 13(1), 121.
  • Kreger J, Garcia J, Zhang H, Komarova NL, Wodarz D, Levy DN (2021) Quantifying the dynamics of viral recombination during free virus and cell-to-cell transmission in HIV-1 infection. Virus Evolution 7(1) veab026
  • Wodarz D. and Komarova NL (2020) Mutant evolution in spatially structured and fragmented expanding populations. Genetics 216, pp.191-203
  • Wodarz, D., Stipp, S., Hirshleifer, D., & Komarova, N. L. (2020). Evolutionary dynamics of culturally transmitted, fertility-reducing traits. Proceedings of the Royal Society B, 287(1925), 20192468.
  • Wodarz D., Levy D.N. & Komarova N.L. (2019) Multiple infection of cells changes the dynamics of basic viral evolutionary processes. Evolution Letters, 3-1: 104–115
  • Wodarz, D., Goel, A., Komarova, N.L. (2017) Effect of cell cycle duration on somatic evolutionary dynamics. Evolutionary Applications, 10(10), 1121-1129.
  • Rodriguez-Brenes IA, Kurtova AV, Lin C, Lee YC, Xiao J, Mims MP, Chan KS, & Wodarz D. (2017) Cellular hierarchy as a determinant of tumor sensitivity to chemotherapy. Cancer Research, 77(9), 2231-2241.
  • Rodriguez-Brenes IA, Hofacre A, Fan H & Wodarz D (2017) Complex dynamics of virus spread from low infection multiplicities: implications for the spread of oncolytic viruses. PLoS Computational Biology 13(1):e1005241.
  • Burger JA, Li KW, Keating MJ, Sivina M, Amer AM, Garg N, Ferrajoli A, Huang X, Kantarjian H, Wierda WG, O’Brien S, Hellerstein MK, Turner SM, Emson CL, Chen SS, Yan XJ, Wodarz D & Chiorazzi N. (2017) Leukemia cell proliferation and death in chronic lymphocytic leukemia patients on therapy with the BTK inhibitor ibrutinib. JCI insight 26, 2(2):e89904
  • Law KM, Komarova NL, Yewdall AW, Lee RK, Herrera OL, Wodarz D & Chen BK (2016) In Vivo HIV-1 Cell-to-Cell Transmission Promotes Multicopy Micro-compartmentalized Infection. Cell Reports 15(12): 2771-83.
  • Komarova NL, Burger JA & Wodarz D (2014) Evolution of ibrutinib resistance in chronic lymphocytic leukemia (CLL). Proc. Natl. Acad. Sci. USA 111(38): 13906-11.
  • Wodarz D., Garg, N., Komarova, N.L., Benjamini, O., Keating, M.J., Wierda, W.G., Kantarjian, H., James, D., O’Brien, S. & Burger, J.A. (2014) Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib. Blood 123(26):4132-4135
  • Komarova, N.L, Shahriyari, L. & Wodarz D (2014) Complex role of space in the crossing of fitness valleys by asexual populations. J. R. Interface 11(95): 20140014
  • Wodarz, D., Sun, Z., Lau, J. W., Komarova, N. (2013). Nearest neighbor interactions, habitat fragmentation, and the persistence of host-pathogen systems. American Naturalist, 182(3), E94-E111.
  • Rodriguez-Brenes, I., Komarova, N., Wodarz, D. (2013). Tumor growth dynamics: insights into somatic evolutionary processes. Trends in Ecology and Evolution 28(10), 597-604
  • Rodriguez-Brenes, I.A., Komarova, N.L. & Wodarz D. 2011 Evolutionary Dynamics of feedback escape and the development of stem-cell driven cancers. Proc. Natl. Acad. Sci USA 108, 18983-8
  • Komarova NL and Wodarz D 2005 Drug resistance in cancer: principles of emergence and resistance. Proc. Natl. Acad. Sci USA, 102, 9714-9

Biography

Dominik Wodarz obtained his undergraduate degree in Biology at Imperial College London, and received a PhD in Zoology from the University of Oxford. He spent his postdoctoral years as a member of the Institute for Advanced Study in Princeton. Before joining UCSD, he held faculty positions at the Fred Hutchinson Cancer Research Center in Seattle and the University of California Irvine.

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