Piera Pasinelli, PhD
Frances and Joseph Weinberg Professor, Department of Neuroscience
Director, Jefferson Weinberg ALS Center
Vickie and Jack Farber Institute for Neuroscience

Contact
900 Walnut Street
JHN 4th floor
Philadelphia, PA 19107
215-955-8394
215-503-4358 fax
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Piera Pasinelli, PhD
Frances and Joseph Weinberg Professor, Department of Neuroscience
Director, Jefferson Weinberg ALS Center
Vickie and Jack Farber Institute for Neuroscience
Research & Clinical Interests
Neurodegenerative diseases, Amyotrophic Lateral Sclerosis
Research in the laboratory focuses on the study of the cellular and molecular events that lead to motor neuron death in Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig' s disease.
ALS is a typical neurodegenerative disease caused by degeneration and death of motor neurons in the spinal cord, brain stem and motor cortex. This leads to muscular atrophy. Death occurs 3 to 5 years from onset. Currently there is no cure for ALS.
The work we do in the laboratory focuses on one particular form of the disease: familial ALS caused by mutations in the gene encoding for the cytosolic copper-zinc superoxide dismutase (SOD1). We study the molecular mechanism(s) by which mutated SOD1 (mutSOD1) causes motor neuron degeneration. The ultimate goal is to identify potential therapeutic targets.
To this end, work in the laboratory develops in two components:
- Basic research
- Drug screening or translational research
Basic Research
Mutations in SOD1 cause motor neuron death through gain of toxic properties that are not fully delineated. This toxicity impairs multiple cellular functions. Mitochondrial abnormalities and activation of cell death genes are characteristic features of mutSOD1-mediated ALS. Our basic research program studies: a) the molecular switches that, upon mutation, convert SOD1 (normally a pro-survival protein) into a toxic molecule using in vitro biochemical approaches,
b) the pathological mechanisms governing mutSOD1-mediated cell death and mitochondrial dysfunction in neuronal cultures and transgenic animal models.
Drug Screening
What we learn from our basic research gets translated into the development of cell based assays to screen for therapeutics. The goal is to develop drugs to cure or ameliorate the disease.
We use different techniques from basic molecular biology to biochemistry and cell biology. We use cloning, protein electrophoresis, immunoblotting, immunofluorescence and immunoprecipitation techniques, in vitro affinity binding assays and subcellular fractionation to isolate organelles from the spinal cord of ALS mice.
As model systems we use neuronal cell cultures with mutSOD1 and transgenic ALS mice that express the human-mutated SOD1 gene. These mice develop and ALS-like disorder; we follow pathogenic molecular changes in the motor neurons of these mice as disease progresses.
Publications
- C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress
- A mouse model with widespread expression of the C9orf72-linked glycine–arginine dipeptide displays non-lethal ALS/FTD-like phenotypes
- Targeting TNFα produced by astrocytes expressing amyotrophic lateral sclerosis-linked mutant fused in sarcoma prevents neurodegeneration and motor dysfunction in mice
- Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development
- Synaptic dysfunction in amyotrophic lateral sclerosis/frontotemporal dementia: Therapeutic strategies and novel biomarkers