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Faculty Affairs: Faculty Interests Database Davide Trotti, Ph.D.

Weinberg Unit for ALS Research
Mailing Address Contact Information
900 Walnut Street
Philadelphia, Pennsylvania 19107
United States
Phone: 215-955-8416
Fax: 215-503-9128
Post-Doctoral, Brigham and Women's Hospital, Harvard Medical School (1997-2000)

Ph.D., Neurotoxicology, University of Milan, Italy (1997)

M.S., Toxicology, University of Milan, Italy (1991)

B.S., Chemistry and Pharmaceutical Technologies, University of Milan, Italy (1989)
Expertise and Research Interests
Neurobiologist Davide Trotti has a long standing interest in understanding the mechanisms of neuronal cell
death in neurodegenerative diseases.

High affinity glutamate transporters play a crucial role in the process of synaptic transmission and in the control
of excitotoxic cell death. After release and interaction with its receptors, glutamate is removed from the synaptic
cleft by uptake mechanisms. The maintenance of a low concentration of external glutamate is one obvious
function of the glutamate transport systems. This function is crucial, as glutamate becomes neurotoxic when its
extracellular concentration exceeds certain levels. A perturbed function at glutamatergic synapses has been
implicated in many disease states, including brain ischemia, epilepsy and several human neurodegenerative
disorders such as Amyotrophic Lateral Sclerosis (ALS).

Research in Dr. Trotti's laboratory is aimed at studying the molecular mechanisms of excitotoxicity leading to
motor neuron degeneration in amyotrophic lateral sclerosis (ALS). ALS is the most common adult motor neuron
disease and its primary hallmark is the death of motor neurons of the spinal cord which leads to spasticity,
hyper-reflexia, general weakness and muscle atrophy. Failure of respiratory muscles is generally the fatal event,
occurring within 1-5 years of symptoms onset.
Impairment in the glutamate transport system and loss of the glutamate transporter GLT1 (a.k.a.EAAT2) are
pathological events contributing to motor neuron death in ALS. Dr. Trotti's laboratory has accumulated expertise
in the study of molecular mechanisms regulating glutamate transporter activity, expression and trafficking.

Another objective of Dr. Trotti's research is the study of mitochondria and the molecular mechanisms leading to
their impaired physiology in ALS. Mitochondria are one of the main sources of energy production and play a
pivotal role in maintaining neuronal cell alive. A pathology-driven impairment in these organelles may shift the
balance between life and death and lead to neuronal degeneration.

1. Post-translational processing of the glial glutamate transporter EAAT2 in ALS
2. Study of ionic conductances of spinal cord mitochondria in ALS
Other Expertise

1996 Society for Neuroscience, Member

2006 Biophysical Society, Member


Manuscript referee: American Journal of Physiology, Biochimica et Biophysica Acta, Journal of Cerebral Flow
and Metabolism, Journal of Biological Chemistry, Gene, European Journal of Neuroscience, Journal of
Neurochemistry, Brain Research, PNAS, Journal of Neuroscience, Trends in Neuroscience, Neuroscience,
Neurobiology of Disease, Annals of Neurology, Journal of Experimental Neurology

Amyotrophic Lateral Sclerosis, Neurodegeneration, Excitotoxicity, Mitochondria, glutamate, pharmacoresistance, RNA
English, Italian
  • Volterra A, Trotti D, Cassutti P, Tromba C, Galimberti R, Lecchi P, Racagni G. A role for the arachidonic acid cascade in fast synaptic modulation: ion channels and transmitter uptake systems as target proteins. Adv Exp Med Biol. 1992;318:147-58.
  • Volterra A, Trotti D, Cassutti P, Tromba C, Salvaggio A, Melcangi RC, Racagni G. High sensitivity of glutamate uptake to extracellular free arachidonic acid levels in rat cortical synaptosomes and astrocytes. J. Neurochem. 1992;59(2):600-6.
  • Volterra A, Trotti D, Tromba C, Floridi S, Racagni G. Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes. J Neurosci. 1994;14(5 Pt 1):2924-32.
  • Volterra A, Trotti D, Racagni G. Glutamate uptake is inhibited by arachidonic acid and oxygen radicals via two distinct and additive mechanisms. Mol Pharmacol. 1994;46(5):986-92.
  • Volterra A, Trotti D, Floridi S, Racagni G. Reactive oxygen species inhibit high-affinity glutamate uptake: molecular mechanism and neuropathological implications. Ann N Y Acad Sci. 1994;738:153-62.
  • Volterra A, Trotti D, Bezzi P, Civenni G, Racagni G. [Ca2+] modulates the ratio between cycloxygenase and lipoxygenase metabolism of arachidonic acid in homogenates of hippocampal astroglial cultures. Neurosci Lett. 1995;183(3):160-3.
  • Trotti D, Volterra A, Lehre KP, Rossi D, Gjesdal O, Racagni G, Danbolt NC. Arachidonic acid inhibits a purified and reconstituted glutamate transporter directly from the water phase and not via the phospholipid membrane. J Biol Chem. 1995;270(17):9890-5.
  • Trotti D, Rossi D, Gjesdal O, Levy LM, Racagni G, Danbolt NC, Volterra A. Peroxynitrite inhibits glutamate transporter subtypes. J Biol Chem. 1996;271(11):5976-9.
  • Volterra A, Bezzi P, Rizzini BL, Trotti D, Ullensvang K, Danbolt NC, Racagni G. The competitive transport inhibitor L-trans-pyrrolidine-2, 4-dicarboxylate triggers excitotoxicity in rat cortical neuron-astrocyte co-cultures via glutamate release rather than uptake inhibition. Eur J Neurosci. 1996;8(9):2019-28.
  • Castagna M, Shayakul C, Trotti D, Sacchi VF, Harvey WR, Hediger MA. Molecular characteristics of mammalian and insect amino acid transporters: implications for amino acid homeostasis. J Exp Biol. 1997;200(Pt 2):269-86.
  • Nussberger S, Steel A, Trotti D, Romero MF, Boron WF, Hediger MA. Symmetry of H+ binding to the intra- and extracellular side of the H+-coupled oligopeptide cotransporter PepT1. J Biol Chem. 97;272(12):7777-85.
  • Trotti D, Rizzini BL, Rossi D, Haugeto O, Racagni G, Danbolt NC, Volterra A. Neuronal and glial glutamate transporters possess an SH-based redox regulatory mechanism. Eur J Neurosci. 1997;9(6):1236-43.
  • Coco S, Verderio C, Trotti D, Rothstein JD, Volterra A, Matteoli M. Non-synaptic localization of the glutamate transporter EAAC1 in cultured hippocampal neurons. Eur J Neurosci. 1997;9(9):1902-10.
  • Trotti D, Nussberger S, Volterra A, Hediger MA. Differential modulation of the uptake currents by redox interconversion of cysteine residues in the human neuronal glutamate transporter EAAC1. Eur J Neurosci. 1997;9(10):2207-12.
  • Castagna M, Shayakul C, Trotti D, Sacchi VF, Harvey WR, Hediger MA. Cloning and characterization of a potassium-coupled amino acid transporter. Proc Natl Acad Sci U S A. 1998;95(9):5395-400.
  • Trotti D, Danbolt NC, Volterra A. Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration? Trends Pharmacol Sci. 1998;19(8):328-34.
  • Civenni G, Bezzi P, Trotti D, Volterra A, Racagni G. Inhibitory effect of the neuroprotective agent idebenone on arachidonic acid metabolism in astrocytes. Eur J Pharmacol. 1999;370(2):161-7.
  • Trotti D, Rolfs A, Danbolt NC, Brown RH, Hediger MA. SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Nat Neurosci. 1999;2(5):427-33.
  • Cunnane SC, Trotti D, Ryan MA. Specific linoleate deficiency in the rat does not prevent substantial carbon recycling from [(14)C]linoleate into sterols. J Lipid Res. 2000;41(11):1808-11.
  • Gegelashvili G, Robinson MB, Trotti D, Rauen T. Regulation of glutamate transporters in health and disease. Prog Brain Res. 2001;132:267-86.
  • Trotti D, Aoki M, Pasinelli P, Danbolt NC, Brown RH, Hediger MA. Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired glutamate clearance capacity. J Biol Chem. 2001;276(1):576-82.
  • Trotti D, Peng JB, Dunlop J, Hediger MA. Inhibition of the glutamate transporter EAAC1 expressed in Xenopus oocytes by phorbol esters. Brain Res. 2001;914(1-2):196-203.
  • Trotti D. A role for glutamate transporters in neurodegenerative diseases. Adv Exp Med Biol. 2002;513:225-48.
  • Marciani P, Trotti D, Hediger MA, Monticelli G. Modulation of DMT1 activity by redox compounds. J Membr Biol. 2004;197(2):91-9.
  • Pasinelli P, Belford ME, Lennon N, Bacskai BJ, Hyman BT, Trotti D, Brown RH. Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. Neuron. 2004;43(1):19-30.
  • Boston-Howes W., Gibb SL., Williams EO, Pasinelli P, Brown RH, Trotti D. Caspase-3 cleaves and inactivates the glutamate transporter EAAT2. J.Biol.Chem. 2006; 281:14076-84.
  • Gibb SL., Boston-Howes W., Lavina SZ., Gustincich S., Brown RH., Pasinelli P., Trotti D. A caspase-derived fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to PML nuclear bodies in ALS. J. Biol. Chem. 2007; 282:32480-90.
  • Boston-Howes W., Williams E.O., Bogush A., Scolere M., Pasinelli P., Trotti D. Nordihydroguaiaretic acid increases glutamate uptake in vivo and in vitro: therapeutic implication for amyotrophic lateral sclerosis. Exp. Neurol. 2008; 213:229-237.
  • Foran E. & Trotti D. Glutamate transporters and the excitotoxic pathway to motor neuron degeneration in ALS. Antioxid Redox Signal. 2009 Jul;11(7):1587-602.

Last Updated by Brian Borowski: Wednesday, April 28, 2010 2:25:13 PM

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