Francesca Bartolini, PhD

Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Pathology & Cell Biology at CUMC

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

Languages

  • Italian

Credentials & Experience

Education & Training

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

Honors & Awards

2012 - Alzheimer’s Association Young Investigator Award (PI)
2013 - Schaefer Research Scholar Award (PI)
2013 - Alzheimer's Association New Investigator Research Grant (PI)
2015 - BrightFocus Foundation Standard Award (PI)
2015 - Thomson Innovation Award (co-PI with Dr. Franck Polleux)

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

  • the regulation and function of the microtubule cytoskeleton
  • molecular and cellular biology of neurodegeneration

Grants

THOMSON INNOVATION AWARD (co-PI with Dr. Franck Polleux)

Project Dates: Nov 2015 to Nov 2017

THOMSON INNOVATION AWARD (co-PI with Dr. Guido Cavaletti)

Project Dates: Nov 2017 to Nov 2018

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

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 

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

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 

Shern J.F., Sharer J.D., Pallas D., Bartolini F., Cowan N.J., Reed M.S., Pohl J and Kahn R. – “ Cytosolic Arl2 is complexed with cofactor D and PP2A” - J Biol Chem, 2003, 278 (42): 40829-40836 

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 

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)

Bartolini F. and Gundersen G.G. “Organization of non-centrosomal microtubule arrays”, J Cell Sci, 2006, 119(20): 4155-4163 

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., 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)

Bartolini F. and Gundersen G.G. “Formins and microtubules”, Bioch Bioph Acta - Molecular Cell Research for Special Issue: Formins, 2010, 1803(2): 164-173 

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

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

Pianu B., Lefort R., Toubier E., and Bartolini F. “Amyloid-beta1-42 peptide regulates microtubule stability independently of tau”- J Cell Sci, 2014 Jan 14. 

Morris E., Nader G., Ramalingam N., Bartolini F., and Gundersen G.G. “Kif4 interacts with EB1 and stabilizes microtubules downstream of Rho-mDia in migrating fibroblasts”- Plos One, 2014, 9(3): e91568.

Bartolini F., Andrés-Delgado L., 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 March 30.

Kawamura A., Washington I., Mihai DM, Bartolini F., Gundersen G.G., Mark M.T. and Nakanishi K. “Identification of ginkgolide targets in brain by photoaffinity labeling”- Chem Biol Drug Des, 2016, Oct 15.

Qu X, Yuan FN, Corona C, Pasini S, Pero ME, Gundersen GG, Shelanski ML, Bartolini F. "Stabilization of dynamic microtubules by mDia1 drives Tau-dependent Aβ1-42 synaptotoxicity" -  J Cell Biol. 2017 Sep 6. pii: jcb.201701045. doi: 10.1083/jcb.201701045. [Epub ahead of print] PMID: 28877993 [PubMed - as supplied by publisher]