Faculty Affairs: Faculty Interests Database Davide Trotti, Ph.D.
Jefferson Weinberg ALS Center
Vickie and Jack Farber Institute for Neuroscience
|Mailing Address||Contact Information|
900 Walnut Street
Philadelphia, Pennsylvania 19107
Personal Web Site
|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|
My research focuses on the mechanisms of neuronal death in amyotrophic lateral sclerosis (ALS). Early in my
career, I reported that the astroglia glutamate transporter EAAT2 (GLT1) was selectively inactivated by the toxic
gain-of-function of ALS-linked mutant SOD1 proteins (Trotti D. et al. SOD1 mutants linked to ALS selectively
inactivate a glial glutamate transporter. Nat. Neurosci. 1999; 2:427-33). These studies laid the groundwork for a
comprehensive research program that aims to understand cell and non-cell autonomous mechanisms of
neurodegeneration in ALS. As an integral component of this program, my laboratory was first to identify the
phenomenon of ABC transporter-mediated pharmacoresistance in ALS, a critical obstacle to successful
pharmacotherapy for ALS. We continue our research to decipher mechanisms by which ALS triggers
pharmacoresistance, having the overarching objective of increasing the efficacy of ALS drug therapies. Over the
years, I successfully cooperated with many collaborators from different national and international institutions as
attested by the many letters of collaboration attached in appendix to this application; therefore I know the
importance of frequent communication among researchers and of constructing a research plan that incorporates
creativity as well as scientific impact. I am currently the Director of Research of the Jefferson Weinberg ALS
Center, a comprehensive ALS Center. Throughout my career, I have published numerous peer-reviewed articles
(with >4,000 citations total). Underscoring the rigor and reproducibility of our work, our most prominent
discovery, that the glutamate transporter EAAT2 is inactivated in ALS, has been replicated by multiple
independent laboratories worldwide. My laboratory has uninterruptedly been supported by NIH grants since
2002, when I started my academic career as independent investigator. I was also able to secure non-federal
support, including four research grants from MDA and one multi-PI grant from Target ALS at Columbia
University. I served as chartered member on two NIH study sections (CDIN, NOMD) in addition to participating
as ad hoc reviewer to various SEPs and DoD study sections. Mentorship is a major component of my laboratory
efforts. Several PhD students have graduated from my laboratory and taken post-doctoral positions or
equivalent positions in biomedical companies. In essence, I developed a solid, well-funded translational
research program focused on understanding the mechanisms of neurodegeneration in ALS and translating
discoveries into potential novel therapeutic approaches.
CONTRIBUTION TO SCIENCE
1. Transcending excitotoxicity: a non-conventional role for the astroglial glutamate transporter EAAT2 in ALS.
2. Mutant SOD1 and Bcl2 in ALS: partners in crime.
3. A stumbling block on the road to a successful pharmacotherapy for ALS.
4. Arginine-rich repeats are at the core of the problems in ALS/FTD.
Google Scholar Profile:
MEMBERSHIP IN SCIENTIFIC SOCIETIES:
Society for Neuroscience, American Society for Neurochemistry
|Amyotrophic Lateral Sclerosis, Neurodegeneration, Excitotoxicity, pharmacoresistance, C9orf72|
Last Updated by Brian Borowski: Wednesday, April 28, 2010 2:25:13 PM