Faculty Affairs: Faculty Interests Database Davide Trotti, Ph.D.
Weinberg Unit for ALS Research
|Mailing Address||Contact Information|
900 Walnut Street
Philadelphia, Pennsylvania 19107
|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.
CURRENT RESEARCH PROGRAMS:
1. Post-translational processing of the glial glutamate transporter EAAT2 in ALS
2. Study of ionic conductances of spinal cord mitochondria in ALS
|MEMBERSHIP IN SCIENTIFIC SOCIETIES:
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|
Last Updated by Brian Borowski: Wednesday, April 28, 2010 2:25:13 PM