- Department of Molecular Biosciences, School of Veterinary Medicine
Mitochondrial disease and therapy
Mitochondrial Pathomechanisms (sick mitochondria) and potential therapeutics (small molecules to make them better). Mitochondria are central to bioenergy and metabolism, and small defects can cause big problems. Mitochondrial defects occur in rare neurodegenerative orphan disease like Friedreich's Ataxia and Leber's Hereditary Optic Neuropathy, and more common neurodegenerative diseases like Alzheimer's. Because mitochondrial defects can contribute to neurodegeneration, we have screened for small molecules that ameliorate these neurodegenerative consequences.
We find that For Two main foci are mitochondrial neurodegenerative diseases, Friedreich's ataxia, and Leber's hereditary optic neuropathy. In both diseases there is an inherited mitochondrial defect that causes neurodegeneration. We study the pathophysiological mechanism using cell and animal models of the disease, RNAseq, microarray, QRTPCR, and biochemical assays. In the last 4 years we used mitodisease cell models to screen for drugs with therapeutic potential. We have also determined anti-aging mechanisms of animals with decreased Shc proteins, and identified molecules that cause beneficial Shc inhibition.
Cytoprotective Shc inhibition for degenerative disease
Genetic depletion of Shc proteins in mice causes protection from toxic stress from metabolic challenge (a high fat diet), toxic challenge (alcohol and other toxins), and neurodegenerative stress (Alzheimer's, MS and ALS). We have done high throughput drug screenin if small molecules to recently identify the first small molecule Shc inhibitor, idebenone, and find that it is both hepatoprotective and neuroprotective, in multiple liver disease and neurodegenerative models.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Integrative Genetics and Genomics
- Molecular, Cellular and Integrative Physiology
- Pharmacology and Toxicology (PTX)
- Integrative Pathobiology
Specialties / Focus
- Mitochondrial Pharmacology
- Shc Pharmacology
- Drug Discovery and Development
- Drug testing in Animal Models of Disease
- VMD 405 GI/Metabolism, Spring
- Genetics 201A, Mitochondrial Genetics
- PTX 202, Pharmacology & Toxicology
- 3rd floor VM3B building, located at 1089 Veterinary Medicine Drive, Davis, CA. http://Cortopassilab.com
- Cortopassi lab: see website to know what we look like
Honors and Awards
- Zumberge Faculty Award 1992, USC
- Pfizer Research Award, 2010
- AAAS Fellow, 2015
- Society for Neuroscience
- 1981 BA Biology Stanford University
- 1988 PhD Biochemistry University of California, Berkeley
- 1992 Postdoctoral Research - Molecular Biology University of Southern California
see our website www.Cortopassilab.com for all pubs.