Francesca Bartolini, PhD

Profile Headshot

Overview

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

Email: fb2131@cumc.columbia.edu

Academic Appointments

  • Assistant Professor of Pathology & Cell Biology at CUMC

Languages

  • Italian

Credentials & Experience

Education & Training

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

Honors & Awards

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.

Research Interests

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

Grants

Sept 2020- August 2022 NIH/NINDS R21 NS120076-01 (PI) “Pathogenic Role of D2 tubulin in Peripheral Neuropathy”

July 2016- June 2021 NIH/NIA RO1 AG050658 (PI), “Pathogenic role for formin mediated microtubule stabilization pathways in Alzheimer’s disease”

July 2018- June 2020 Thomson Innovation Award (co-PI with Dr. Cavaletti)
“Investigating the Pathogenic Role of Tubulin PTM Induction in CIPN”, (NCE)

Sept 2018- Aug 2020 Thomson Innovation Award (co-PI with Dr. Wes Grueber)
“Establishing a translational strategy to identify neuroprotective pathways for CIPN: linking basic research outcomes to the development of an in vivo translational strategy using Drosophila and mouse models of CIPN”, (NCE)

PATHOGENIC ROLE FOR FORMIN MEDIATED MICROTUBULE STABILIZATION PATHWAYS IN ALZHEIMERS DISEASE (Federal Gov)

Jun 1 2016 - May 31 2021

FORMIN-MEDIATED STABILIZATION OF DYNAMIC MICROTUBULES IN THE PATHOGENESIS OF EARLY-ONSET FAMILIAL ALZHEIMERS DISEASE (Federal Gov)

Aug 1 2018 - Jun 30 2020

FORMIN-INDUCED STABLE MICROTUBULES IN ALZHEIMER S DISEASE (Private)

Jul 1 2015 - Jun 30 2018

ALZHEIMER S DISEASE RESEARCH CENTER AT COLUMBIA UNIVERSITY (Federal Gov)

Jun 1 2010 - May 31 2015

REGULATION OF MICROTUBULE DYNAMICS BY AMYLOID-BETA PEPTIDE (Private)

Apr 1 2013 - Mar 31 2015

REGULATION OF MICROTUBULES BY RHO GTPASES (Federal Gov)

Dec 1 2009 - Nov 30 2013

MECHANISMS OF INTEGRIN-MICROTUBULE CROSS-TALK (Federal Gov)

Aug 1 2003 - Jul 31 2011

Selected Publications

Selected Publications

Dhanwani R., Pham J., Ramamoorthy Premlal A.L., Frazier A., Kumar A., Pero M.E., Bartolini F., Rezende Dutra J., Marder K., Bjoern P., Sulzer ., Sette A., Lindestam Arlehamn C. "T cell responses to neural autoantigens are similar in Alzheimer's disease patients and age-matched healthy controls"- Frontiers in Neuroscience, section Neurodegeneration (in press).

Stephen D. Carter, Cheri M. Hampton, Robert Langlois, Roberto Melero, Zachary J. Farino, Wen Li, Robert A. Grassucci, Stephanie Siegmund, Joshua Pemberton, Travis J. Morgenstern, Jenny I. Aguilar, Elana S. Levy, Nili L. Greenberg, William J. Rice, Christoph Wigge, Maïté Courel, Robin J. Freyberg, Estela Area-Gomez, Bartolini F., Peter Walter, Tamas Balla, Jose-Maria Carazo, Grant J. Jensen, Joachim Frank, Zachary Freyberg. "Ribosome-Associated Vesicles: a dynamic vesicular endoplasmic reticulum in secretory cells"- Science Advances 2020. doi: 10.1126/sciadv.aay 9572.

Pinto-Costa R., Sousa S.C., Leite S. C., Nogueira-Rodrigues J., Ferreira da Silva T., Marques J., Costa A.C., Liz M.A., Bartolini F., Brites P., Costell M., Fässler R., and Sousa M.M. "Profilin1 delivery tunes cytoskeleton dynamics towards CNS axon regeneration"- J Clin Invest. 2020 Jan 16. pii: 125771. doi: 10.1172/JCI125771.

Qu X., Kumar A., Blockus H., Waites C., and Bartolini F*. "Activity-dependent nucleation of dynamic microtubules at presynaptic boutons controls neurotransmission"- Curr Biol, 2019, Dec 16;29(24):4231-4240.e5. doi: 10.1016/j.cub.2019.10.049. (Dispatch in Curr Biol, 2019, DOI:https://doi.org/10.1016/j.cub.2019.11.011, and recommended in F1000Prime: Sedensky M and Zimin P: 16 Dec 2019; 10.3410/f.737035724.793568574, Gupton S: 12 Feb 2020; 10.3410/f.737035724.793570673 and Chapman E and Vevea J: 20 Feb 2020; 10.3410/f.737035724.793571031).

Teoh J., Subramanian N., Pero M.E., Bartolini F., Amador A., Kanber A., Williams D., Petri S.,Yang M., Allen A.S., Beal J., Haut S.R., Frankel W.N."Arfgef1 haploinsufficiency in mice reduces membrane surface postsynaptic GABAA receptors through dysregulation of endosomal membrane transport"- Neurobiol Dis, 2019, 134:104632.

Qu X., F.N. Yuan, C. Corona, S. Pasini, Gundersen G.G., M. Shelanski, and Bartolini F*. "Stabilization of dynamic microtubules by mDia1 drives Tau-dependent Aβ1-42 synaptotoxicity" - J Cell Biol, 2017, 216(10):3161-3178. (Featured article in a special collection by J of Cell Biol of Reviews in Neurodegeneration for ASCB 2017)

Bartolini F., Andrés-Delgado L., Qu X., Nik S., Ramalingam N., Alonso M.A., and Gundersen G.G. "An mDia1/INF2 activation cascade facilitated by IQGAP1 regulates stable microtubules in migrating cells"- MBoC, 2016, 27(11): 1797-1808.
8) Pianu B., Lefort R., Toubier E., and Bartolini F*. "Amyloid-beta1-42 peptide regulates microtubule stability independently of tau"- J Cell Sci, 2014, 127(5):1117-27.

Andres-Delgado L., et al., Olga M. Anton, Bartolini F., Gundersen G.G., and Alonso A.M. "The formin INF2 mediates the formation of arrays of detyrosinated microtubules necessary for reorientation of the centrosome to the immunological synapse of T lymphocytes"- J Cell Biol, 2012, 198(6):1025-37.

Bartolini F., Ramalingam N., and Gundersen G.G. "The formin mDia1 is released from actin filaments to stabilize microtubules"- MBoC, 2012, 23(20):4032-40.

Okada K., Bartolini F., Deaconescu A., Moseley J. B., Dogic Z., Grigorieff N., Gundersen G.G., and Goode B. L. "The tumor suppressor APC is a potent nucleator of actin assembly that synergizes with formins"- J Cell Biol, 2010, 89(7): 1087-1096, (In focus in J Cell Biol, 2010, 89(7): 1055).

Bartolini F., Moseley J.B., Schmoranzer J., Goode B.L., and Gundersen G.G. "The formin mDia stabilizes microtubules independently of its actin nucleation activity"- J Cell Biol, 2008, 181(3): 523-536, (Dispatch in Curr Biol, 2008, 18(14): 605-608).

Moseley J. B., Bartolini F., Okada K., Wen Y, Gundersen G.G., and Goode B.L. "Regulated binding of Adenomatous polyposis coli (APC) protein to actin"- J Biol Chem, 2007, 282(17): 12661-12668.

Bartolini F., Tian G., Piehl M., Cassimeris L., Lewis S. and Cowan N.J. - "Identification of a novel-tubulin destabilizing protein related to tubulin-chaperone cofactor E" - J Cell Sci, 2005, 118: 1197-1207, (Research Focus in Trends in Cell Biol, 2005, 15(11): 571-573).

Bloom J., Amador V., Bartolini F., De Martino G., and Pagano M. - "Triggering proteosome-mediated degradation of p21 via the ubiquitin system" - Cell, 2003, 115(1): 71-82.

Grayson C, Bartolini F., Chapple J.P., Willison K.R., Bhamidipati A., Lewis S.A., Luthert P.J., Hardcastle A.J., Cowan N.J. and Cheetham M.E. - "Localization in the human retina of the X-linked retinitis pigmentosa protein RP2, its homologue cofactor C and the RP2 interacting protein Arl3" - Hum Mol Genet, 2002, 11(24): 3065-3074.

Martin-Benito J., Boskovic J., Gomez-Puertas P., Carrascosa J.L., Simons C., Lewis S.A., Bartolini F., Cowan N.J. and Valpuesta J.M. - "Structure of eukariotic Prefoldin and of its complexes with unfolded actin and the cytosolic chaperonin CCT" - EMBO J, 2002, 21(23): 6377-6386.

Bartolini F., Bhamidipati A., Thomas S., Schwahn U., Lewis S.A., Cowan N.J.- "Functional overlap between retinitis pigmentosa 2 protein and the tubulin-specific chaperone Cofactor C" - J Biol Chem, 2002, 277(17): 14629-14634.

Peer Reviewed Reviews:

1) Bartolini F. and Gundersen G.G. "Organization of non-centrosomal microtubule arrays", J of Cell Sci, 2006, 119(20): 4155-4163.
2) Bartolini F. and Gundersen G.G. "Formins and microtubules", Bioch Bioph Acta - Molecular Cell Research for Special Issue: Formins, 2010, 1803(2): 164-173.

Preprinted Articles, Invited Reviews & Editorials:

1) Shin G.J., Pero M.E., Hammond L.A., Burgos A., Galindo S.E., Bartolini F.*, and W.B. Grueber* "Integrins protect nociceptive neurons in models of paclitaxel-mediated peripheral sensory neuropathy"- (under submission as revised manuscript to PNAS) (*co-senior PIs) bioRxiv 829655; doi: https://doi.org/10.1101/829655.
2) Pero M.E., Meregalli C., Qu X., Kumar A, Shorey M., Rolls M., Tanji K., Brannangan T.H., Alberti P., Fumagalli G., Monza L., Cavaletti G. and Bartolini F*. "Pathogenic role of Delta-2 tubulin in bortezomib induced peripheral neuropathy"- (resubmitted as revised manuscript to PNAS). bioRxiv 721852; doi: https://doi.org/10.1101/721852.
3) Bartolini F*., Qu X., Julie Parato, Leung J., and Cassimeris L. "Tubulin and microtubules: the neuron's Achille's heel"- (invited Review in Trends in Neuroscience) (*corresponding author).
4) Guest Editor of a Special Issue on "Microtubules: multiple roles in healthy neurons and in neurological disease"- Neuroscience Letters.
5) Waites C. and Bartolini F*. "Microtubule-dependent regulation of synaptic function"- (invited Review in Current Opinion in Neurobiology)
6) Co-guest Editor with Guido Cavaletti of a Special Issue on "Tubulin and axonal transport disturbances in CNS and PNS diseases"- Experimental Neurology