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

  • 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

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. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. van Haren J, Adachi LS, Wittmann T. Optogenetic Control of Microtubule Dynamics. Methods Mol Biol. 2020; 2101:211-234.  View on PubMed
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. Kenific CM, Wittmann T, Debnath J. Autophagy in adhesion and migration. J Cell Sci. 2016 10 15; 129(20):3685-3693.  View on PubMed
  15. Ettinger A, van Haren J, Ribeiro SA, Wittmann T. Doublecortin Is Excluded from Growing Microtubule Ends and Recognizes the GDP-Microtubule Lattice. Curr Biol. 2016 06 20; 26(12):1549-1555.  View on PubMed
  16. Kenific CM, Stehbens SJ, Goldsmith J, Leidal AM, Faure N, Ye J, Wittmann T, Debnath J. NBR1 enables autophagy-dependent focal adhesion turnover. J Cell Biol. 2016 Feb 29; 212(5):577-90.  View on PubMed
  17. Prochazka J, Prochazkova M, Du W, Spoutil F, Tureckova J, Hoch R, Shimogori T, Sedlacek R, Rubenstein JL, Wittmann T, Klein OD. Migration of Founder Epithelial Cells Drives Proper Molar Tooth Positioning and Morphogenesis. Dev Cell. 2015 Dec 21; 35(6):713-24.  View on PubMed
  18. Lane AB, Strzelecka M, Ettinger A, Grenfell AW, Wittmann T, Heald R. Enzymatically Generated CRISPR Libraries for Genome Labeling and Screening. Dev Cell. 2015 Aug 10; 34(3):373-8.  View on PubMed
  19. Basu S, Sladecek S, Pemble H, Wittmann T, Slotman JA, van Cappellen W, Brenner HR, Galjart N. Acetylcholine receptor (AChR) clustering is regulated both by glycogen synthase kinase 3β (GSK3β)-dependent phosphorylation and the level of CLIP-associated protein 2 (CLASP2) mediating the capture of microtubule plus-ends. J Biol Chem. 2014 Oct 31; 289(44):30857-30867.  View on PubMed
  20. Liz MA, Mar FM, Santos TE, Pimentel HI, Marques AM, Morgado MM, Vieira S, Sousa VF, Pemble H, Wittmann T, Sutherland C, Woodgett JR, Sousa MM. Neuronal deletion of GSK3β increases microtubule speed in the growth cone and enhances axon regeneration via CRMP-2 and independently of MAP1B and CLASP2. BMC Biol. 2014 Jun 12; 12:47.  View on PubMed

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