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Dominik Wodarz

Research

The Wodarz lab works on mathematical and computational models of biological processes, with an emphasis on biomedical applications. Evolutionary dynamics is a unifying theme across different areas of investigation. These include the following:

  • Dynamics of cancer and its treatment. Mathematical models are developed that describe the clonal evolution of cells in healthy tissue, the growth and evolution of cancer cells during carcinogenesis, and the response of cancers to therapies. This includes modeling resistance evolution, and how resistance-induced treatment failure can be prevented. Recent research has focused particularly on the hematopoietic system and on hematopoietic malignancies, but has also included a number of solid tumors. One of the goals of this work is to use the mathematical models to develop patient-specific predictions of treatment outcomes, by applying models to clinical data through collaborations.
  • Dynamics of virus infections and immune responses. Mathematical models are developed that describe the complex interactions between in vivo virus spread and anti-viral immune responses. A long-standing interest has been the interactions between viral infections and cytotoxic T lymphocyte (CTL) responses, particularly in the context of human immunodeficiency virus (HIV), and experimental mouse infections. The goal is to better understand correlates of CTL-mediated virus control, to study how virus evolution can influence the course of disease, and to analyze treatment interventions to improve virus control in the context of evolving virus populations.
  • Evolutionary theory. Evolutionary processes are a recurrent theme in the biomedical applications. To complement this work, new evolutionary theory is developed. Particular emphasis is placed on the role of spatially restricted population growth on evolutionary outcomes, such as the emergence of different kinds of mutants or the crossing of fitness valleys. More generally, the goal is to understand how assumptions about population structure influence evolutionary dynamics, with special relevance to bacterial and eukaryotic cell populations.

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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