Research Summary

Modern molecular biology presents us with a growing list of molecules that build a living cell. However, how the diverse activities of these molecules are coordinated in space and time to generate functional and dynamic cell biology is an increasingly complex and essentially unresolved question. Intracellular dynamics are coordinated by the cytoskeleton, and we are interested in how microtubules, a highly dynamic filament system inside eukaryotic cells, control cell behavior and morphogenesis in human tissue culture models, such as cancer and hiPSC-derived neurons by using advanced microscopy, optogenetics and microfabrication.

In ongoing projects, we ask how Doublecortin, a microtubule-associated protein frequently mutated in neurodevelopmental cortical malformations, and related proteins control microtubule function in developing neurons. We also develop optogenetic tools to control intracellular protein activities with high spatial and temporal accuracy aiming to guide cell division and neuronal development to engineer synthetic neuron network modules, and we develop microscopy to better visualize cancer and neuronal cell dynamics in physiological 3D environments.

Research Funding

  • February 1, 2024 - January 31, 2027 - Quantitative analysis and manipulation of chromosome dynamics in cancer organoids , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R61CA278518
  • June 15, 2018 - February 28, 2023 - Probing Microtubule Function in Neuronal Development , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01NS107480
  • September 20, 2020 - September 19, 2021 - Wide-field super-resolution spinning disk confocal microscope , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10OD028611
  • June 10, 2017 - May 31, 2020 - Dissecting protein activities by reversible photo-inactivation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21CA224194
  • May 1, 2008 - December 31, 2017 - Microtubule dynamics during cell polarity and migration , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM079139
  • September 1, 2010 - August 31, 2015 - Light-activated proteolysis as a tool to analyze intracellular protein function , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM094819
  • May 27, 2010 - May 26, 2011 - Spinning disk confocal / FRAP microscope for quantitative live cell imaging , Principal Investigator . Sponsor: NIH, Sponsor Award ID: S10RR026758

Education

  • University of Basel, Switzerland M.S. 11/90-10/94 Biology
  • University of Heidelberg, Germany Ph.D. 09/95-05/99 Cell Biology
  • EMBL Heidelberg, Germany Postdoc 06/99-06/00 Cell Biology
  • The Scripps Research Institute, La Jolla Postdoc 08/00-10/05 Cell Biology/Microscopy

Honors & Awards

  • 2003 1st prize, Nikon Small World Photomicrography Competition, (3rd in 2004; 5th in 2002)
  • 2007 American Heart Association Scientist Development Award
  • 2010 NIH/NIGMS Eureka Award

Selected Publications

  1. Viola G, Ibrahim YW, Jacobs KA, Lemière J, Kutys ML, Wittmann T. Quantitative comparison of fluorescent proteins using protein nanocages in live cells. J Cell Sci. 2025 May 15; 138(10).  View on PubMed
  2. Dema A, Charafeddine RA, van Haren J, Rahgozar S, Viola G, Jacobs KA, Kutys ML, Wittmann T. Doublecortin reinforces microtubules to promote growth cone advance in soft environments. Curr Biol. 2024 Dec 16; 34(24):5822-5832.e5.  View on PubMed
  3. Liboy-Lugo JM, Espinoza CA, Sheu-Gruttadauria J, Park JE, Xu A, Jowhar Z, Gao AL, Carmona-Negrón JA, Wittmann T, Jura N, Floor SN. G3BP isoforms differentially affect stress granule assembly and gene expression during cellular stress. Mol Biol Cell. 2024 Nov 01; 35(11):ar140.  View on PubMed
  4. Viola G, Jacobs KA, Lemière J, Kutys ML, Wittmann T. Quantitative Comparison of Monomeric StayGold Variants Using Protein Nanocages in Living Cells. bioRxiv. 2024 Sep 17.  View on PubMed
  5. Dema A, Charafeddine RA, van Haren J, Rahgozar S, Viola G, Jacobs KA, Kutys ML, Wittmann T. Doublecortin reinforces microtubules to promote growth cone advance in soft environments. bioRxiv. 2024 Feb 29.  View on PubMed
  6. Liboy-Lugo JM, Espinoza CA, Sheu-Gruttadauria J, Park JE, Xu A, Jowhar Z, Gao AL, Carmona-Negrón JA, Wittmann T, Jura N, Floor SN. Protein-protein interactions with G3BPs drive stress granule condensation and gene expression changes under cellular stress. bioRxiv. 2024 Feb 07.  View on PubMed
  7. Dema A, Charafeddine R, Rahgozar S, van Haren J, Wittmann T. Growth cone advance requires EB1 as revealed by genomic replacement with a light-sensitive variant. Elife. 2023 01 30; 12.  View on PubMed
  8. Stormo AED, Shavarebi F, FitzGibbon M, Earley EM, Ahrendt H, Lum LS, Verschueren E, Swaney DL, Skibinski G, Ravisankar A, van Haren J, Davis EJ, Johnson JR, Von Dollen J, Balen C, Porath J, Crosio C, Mirescu C, Iaccarino C, Dauer WT, Nichols RJ, Wittmann T, Cox TC, Finkbeiner S, Krogan NJ, Oakes SA, Hiniker A. The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity. J Cell Biol. 2022 04 04; 221(4).  View on PubMed
  9. Dema A, van Haren J, Wittmann T. Optogenetic EB1 inactivation shortens metaphase spindles by disrupting cortical force-producing interactions with astral microtubules. Curr Biol. 2022 03 14; 32(5):1197-1205.e4.  View on PubMed
  10. Dema A, Rahgozar S, Siquier L, van Haren J, Wittmann T. Controlling Cell Shape and Microtubule Organization by Extracellular Matrix Micropatterning. Methods Mol Biol. 2022; 2430:467-481.  View on PubMed
  11. Webb BA, Aloisio FM, Charafeddine RA, Cook J, Wittmann T, Barber DL. pHLARE: a new biosensor reveals decreased lysosome pH in cancer cells. Mol Biol Cell. 2021 01 15; 32(2):131-142.  View on PubMed
  12. Zhang J, Velmeshev D, Hashimoto K, Huang YH, Hofmann JW, Shi X, Chen J, Leidal AM, Dishart JG, Cahill MK, Kelley KW, Liddelow SA, Seeley WW, Miller BL, Walther TC, Farese RV, Taylor JP, Ullian EM, Huang B, Debnath J, Wittmann T, Kriegstein AR, Huang EJ. Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency. Nature. 2020 12; 588(7838):459-465.  View on PubMed
  13. Wittmann T, Dema A, van Haren J. Lights, cytoskeleton, action: Optogenetic control of cell dynamics. Curr Opin Cell Biol. 2020 10; 66:1-10.  View on PubMed
  14. van Haren J, Adachi LS, Wittmann T. Optogenetic Control of Microtubule Dynamics. Methods Mol Biol. 2020; 2101:211-234.  View on PubMed
  15. Charafeddine RA, Cortopassi WA, Lak P, Tan R, McKenney RJ, Jacobson MP, Barber DL, Wittmann T. Tau repeat regions contain conserved histidine residues that modulate microtubule-binding in response to changes in pH. J Biol Chem. 2019 05 31; 294(22):8779-8790.  View on PubMed
  16. van Haren J, Wittmann T. Microtubule Plus End Dynamics - Do We Know How Microtubules Grow?: Cells boost microtubule growth by promoting distinct structural transitions at growing microtubule ends. Bioessays. 2019 03; 41(3):e1800194.  View on PubMed
  17. van Haren J, Charafeddine RA, Ettinger A, Wang H, Hahn KM, Wittmann T. Local control of intracellular microtubule dynamics by EB1 photodissociation. Nat Cell Biol. 2018 03; 20(3):252-261.  View on PubMed
  18. Webb BA, Dosey AM, Wittmann T, Kollman JM, Barber DL. The glycolytic enzyme phosphofructokinase-1 assembles into filaments. J Cell Biol. 2017 08 07; 216(8):2305-2313.  View on PubMed
  19. Pemble H, Kumar P, van Haren J, Wittmann T. GSK3-mediated CLASP2 phosphorylation modulates kinetochore dynamics. J Cell Sci. 2017 04 15; 130(8):1404-1412.  View on PubMed
  20. Kenific CM, Wittmann T, Debnath J. Autophagy in adhesion and migration. J Cell Sci. 2016 10 15; 129(20):3685-3693.  View on PubMed

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