Francesca Bartolini, PhD

  • Associate Professor of Pathology and Cell Biology
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Overview

Dr. Bartolini is a biologist with a Ph.D. in Biochemistry from NYU. She heads a research laboratory investigating the role of microtubule stability and tubulin post-translational modifications in the onset of neurodegenerative and neuropathic disease.

Email: fb2131@cumc.columbia.edu

Laboratory website: Bartolini Lab

Academic Appointments

  • Associate Professor of Pathology and Cell Biology

Languages

  • English
  • Italian

Credentials & Experience

Education & Training

  • PhD, 2004 Biochemistry, New York University (NYU Medical Center - University Hospital)

Honors & Awards

  • July 2024 - 2024 Velocity Fellow, Columbia University’s Herbert Irving Comprehensive Cancer Center (HICCC)
  • April 2023 - Fellow at Reid Hall in Paris, one of Columbia University Global Centers, FR
  • June 2019 - Fulbright Specialist
  • April 2013 - Schaefer Research Scholar Award for distinguished achievement in human physiology, Columbia University’s College of Physicians and Surgeons, New York

Research

"Reserve your right to think, for even to think wrongly is better than not to think at all" - Hypatia of Alexandria, mathematician and philosopher (370 AD - 415 AD)

Neurons possess extensive tubulin post-translational modifications (PTMs) that are associated with microtubule (MT) longevity, and analyses of mammalian brain and cultured neurons demonstrate enrichment of detyrosinated, acetylated, poly-glutamylated and D2-tubulin subunits. These tubulin PTMs are implicated in the regulation of MT associated proteins (known as MAPs), MT severing enzymes, and binding to motors. Synaptic activation also locally regulates tubulin PTMs associated with MT stability. In addition to stable MTs, emerging studies indicate that dynamic MTs, typically deprived of tubulin PTMs, play key roles in neuronal function. Dynamic MTs polymerize from dendritic shafts into spines, and signaling through neurotransmitter receptors and local calcium entry regulate this process. Invasion of dendritic spines by dynamic MTs can in return affect spine morphology and function by regulating myosin- and kinesin-paired cargo dynamics. Furthermore, presynaptic dynamic MTs are necessary for the delivery of synaptic vesicles to their appropriate sites, and may mediate storage and/or docking /fusion of vesicles at the active zone. Thus, aside from their more conventional role in offering structural support to the neuron, MTs are fine regulators of neuronal homeostasis and synaptic function, and unwanted changes in MT dynamics, stability and/or tubulin PTMs may be involved in the onset of neurodegenerative and neuropathic disease by: ) impairing MT-dependent axonal and dendritic trafficking; 2) disrupting synaptic transmission; 3) interfering with the binding of MT severing enzymes and MAPs. My laboratory studies whether disruption of MT dynamicity and induction of tubulin PTMs is a general property of various neurodegenerative and neuropathic stimuli. In addition, we are particularly interested in the role of formins, a class of proteins with independent functions on the actin and MT cytoskeletons in regulating MT behavior downstream of neuropathogenic pathways. To tackle these questions, we employ biochemical and cell-biological approaches using immortalized non-neuronal cells, primary neuronal cultures and animal models of disease.

Click here to visit my laboratory website.

 

Research Interests

  • Molecular and Cellular Biology of Neurodegeneration
  • the regulation and function of the microtubule cytoskeleton at synapses

Grants

  • Sept 2024-August 2029: NIH/NCI (Bartolini: PI) R01 CA279401-01 “Investigating the Pathogenic Role of Tubulin Post-translational Modifications in CIPN”.
  • July 2024-June 2025: Velocity Award (Bartolini: PI), “The INF2/mDia Axis: Pioneering a Path to Novel Therapies for SHH-Medulloblastoma”.
  • August 2022-July 2027: NIH/NIA RF1 AG050658 (Bartolini: PI), “Pathogenic Roles for Microtubule Stabilization Pathways in Alzheimer’s disease”, (administrative 2 year renewal in 2025).

Selected Publications

Peer Reviewed Articles:
(*) corresponding or co-corresponding author

  • Wojnacki J., Quassollo G., Bordenave M.D., Unsain N., Martinez G.F., Szalai A.M., Pertz O., Gundersen G.G., Bartolini F., Stefani F.D., Caceres A., and Bisbal M. "Dual spatio-temporal regulation of axon growth and microtubule dynamics by RhoA signaling pathways" J Cell Science 2024, J Cell Sci. 2024 Jul 15;137(14):jcs261970. doi: 10.1242/jcs.261970.
  • Kumar A., Larrea D., Pero M.E., Infante P., Conenna M., Shin G.J., Van Elias V., Grueber W.B., Di Marcotullio L., Area-Gomez E., and Bartolini F.*, “MFN2 coordinates mitochondria motility with ?-tubulin acetylation and this regulation is disrupted in CMT2A”- accepted in iScience May 15;27(6):109994. doi: 10.1016/j.isci.2024.10999.
  • Oevel K., Hohensee S., Kumar A., Rosas-Brugada I., Bartolini F., Soykan T. and Haucke V."Rho GTPase signaling and mDia facilitate endocytosis via presynaptic actin" - Elife 2024 Mar 19;12:RP92755. doi: 10.7554/eLife.92755.
  • Sanchini C., Rosito M., Comincini A., De Panfilis S., Bartolini F.*, Di Angelantonio S.* “Functional live-imaging of microtubule dynamics in primary microglia” STAR Protocols 2023 Sep 15;4(3):102499. doi: 10.1016/j.xpro.2023.102499.
  • Rosito M., Sanchini C., Gosti G., Moreno M., De Panfilis S., Giubettini M., Debellis D., Catalano F., Peruzzi G., Marotta R., Indrieri A., De Leonibus E., Ragozzino D., Ruocco G., Di Angelantonio S.*, Bartolini F.* "Reactive microglia and cytokine release entails microtubule remodeling from acentrosomal to centrosomal arrays"- Cell Reports 2023 Feb 13;42(2):112104. doi: 10.1016/j.celrep.2023.112104.
  • Kim Y. A., Blaze J., Winters T., Kumar A., Tein E., Sproul A., Teich A.F., Bartolini F., Akbarian S., Hargus G., Santa-Maria I. "RNA methyltransferase NSun2 deficiency promotes neurodegeneration through epitranscriptomic regulation of tau phosphorylation"- Acta Neuropathol. 2023 Jan;145(1):29-48. doi: 10.1007/s00401-022- 02511-7.
  • Martínez-Hernández J., Parato J., Sharma A., Soleilhac J., Qu X., Tein E., Sproul, Annie Andrieux A., Goldberg Y., Moutin MJ, Bartolini F.* and Leticia Peris*- Crosstalk between acetylation and the tyrosination/detyrosination cycle of α-tubulin in Alzheimer’s disease - Frontiers in Cell and Dev Biol - 2022 Aug 26;10:926914. doi: 10.3389/fcell.2022.926914. eCollection 2022.
  • Orman M, Landis M, Oza A, Nambiar D, Gjeci J, Song K, Huang V, Klestzick A, Hachicho C, Liu SQ, Kamm JM, Bartolini F, Vadakkan JJ, Rojas CM, Vizcarra CL. "Alterations to the broad-spectrum formin inhibitor SMIFH2 modulate potency but not specificity"- Sci Rep. 2022 Aug 8;12(1):13520. doi: 10.1038/s41598-022-17685-z.
  • PPeris L.*, Parato J., Qu X., Soleilhac JM, , Lante F., Kumar A., Pero M.E., Martinez-Hernandez J., Corrao C., Falivelli G., Payet F., Gory-Faure S., Bosc C., Blanca Ramirez M., Sproul A., Brocard J., Di Cara B., Delagrange P., Buisson A., Goldberg Y., Moutin M.J.*, Bartolini F.* and Andrieux A*. “Impaired α-tubulin re-tyrosination leads to synaptic dysfunction and is a feature of Alzheimer's disease”- Brain 2022 Jul 29;145(7):2486-2506. doi: 10.1093/brain/awab436.
  • Eira J., Magalhães J., Macedo N., Pero M.E., Misgeld T., Sousa M.M., Bartolini F., Liz M.A. “Transthyretin promotes axon growth via regulation of microtubule dynamics and tubulin acetylation” – Front Cell Dev Biol 2021 Nov 8;9: 747699.
  • Shin G.J., Pero M.E., Hammond L.A., Burgos A., Kumar A., Galindo S.E., Tanguy L., Bartolini F. and Grueber W.B. “Integrins protect nociceptive neurons in models of paclitaxel-mediated peripheral sensory neuropathy”- PNAS 2021 Apr 13;118(15):e2006050118.
  • Qu X., Kumar A. and Bartolini F.* “Live-imaging of microtubule dynamics at excitatory presynaptic boutons in primary hippocampal neurons and acute hippocampal slices”, STAR Protocols 2021, Feb 21;2(1):100342. doi: 10.1016/j.xpro.2021.100342. eCollection 2021 March.
  • Pero M.E., Meregalli C., Qu X., Shin G.J., Kumar A, Shorey M., Rolls M., Tanji K., Brannangan T.H., Alberti P., Fumagalli G., Monza L., Grueber W.B., Cavaletti G. and Bartolini F.* “Pathogenic role of Delta-2 tubulin in bortezomib induced peripheral neuropathy”- PNAS 2021 Jan 26;118(4):e2012685118
  • Müller-Deku A., Meiring J.C.M., Loy K., Kraus Y., Heise C., Bingham R., Jansen K.I., Qu X., Bartolini F., Kapitein L.C., Akhmanova A., Ahlfeld J., Trauner D., Thorn-Seshold O. "Photoswitchable paclitaxel-based microtubule stabilisers allow optical control over the microtubule cytoskeleton"- Nat Comm 2020 Sep 15;11(1):4640. doi: 10.1038/s41467-020-18389-6.

Peer Reviewed Invited Reviews:

  • Pero M.E., Chowdhury F and Bartolini F.* "Tubulin post-translational modifications in peripheral neuropathies" - (Exp Neurol., 2022 Nov 13;360:114274. doi: 10.1016/j.expneurol.2022.114274 - Special Issue on "Tubulin and axonal transport disturbances in CNS and PNS diseases)
  • Waites C., Xioayi Qu and Bartolini F.* “The synaptic life of microtubules”, Curr Opin Neurobiol, 2021, Apr 16;69:113-123.
  • Parato J. and Bartolini F.* “The microtubule cytoskeleton at the synapse”, Neurosci Lett, 2021, Mar 25:135850. doi: 10.1016/j.neulet.2021.135850.
  • Lieberman O.J., Bartolini F. and Miniaci M.C. "Unveiling the impact of GIRK channels in Alzheimer's disease", Aging-US 2020 Oct 14;12(19):18793-18794.
  • Bartolini F. and Gundersen G.G. “Formins and microtubules”, BBA- Molecular Cell Research for Special Issue: Formins, 2010, 1803(2): 164-173.
  • Bartolini F. and Gundersen G.G. “Organization of non-centrosomal microtubule arrays”, J Cell Sci 2006, 119(20): 4155-4163.

Preprinted Articles, Invited Reviews & Editorials:

  • Wojnacki J., Quassollo G., Bordenave M.D., Unsain N., Martinez G.F., Szalai A.M., Pertz O., Gundersen G.G., Bartolini F., Stefani F.D., Caceres A., Bisbal M. “Dual spatiotemporal regulation of axon growth and microtubule dynamics by RhoA signaling pathways”, bioRxiv 2023.04. 17.537156
  • Kumar A, Larrea D, Pero ME, Infante P, Conenna M, Shin GJ, Grueber WB, Di Marcotullio L, Area-Gomez E, Bartolini F.* “MFN2-dependent recruitment of ATAT1 coordinates mitochondria motility with alpha-tubulin acetylation and is disrupted in CMT2A”, bioRxiv. 2023 Mar 16;2023.03.15.532838. doi: 10.1101/2023.03.15.532838.
  • Co-guest Editor with Guido Cavaletti of a Special Issue on “Tubulin and axonal transport disturbances in CNS and PNS diseases”- Expl Neurol, 2023, 62:114343. doi: 10.1016/j.expneurol.2023.114343
  • Guest Editor of the Special Issue “Microtubules: multiple roles in healthy neurons and in neurological disease”- Neurosci Lett, 2021, https://www.sciencedirect.com/journal/neuroscience-letters/specialissue/ 10NG2MQJ2Q4

For a complete list of publications, please visit PubMed.gov