Maria Figueiredo-Pereira, PhD is the co-principal investigator of this project. The initial studies that led to the development of this project were carried out in her laboratory at Hunter College of CUNY where she is an associate professor of biology. Those studies were funded by a grant from the National Institute of Health/NINDS in which she is the principal investigator. Education: University of Lisbon, Portugal BSc 1970 Biology University of Lisbon, Portugal MSc 1972 Biology New York University PhD 1985 Endocrinology Dr. Figueiredo-Pereira did her thesis work on the identification of the site of action of a gene that controls the age of the onset of maturation in the platyfish, with Dr. Klaus Kallman, a world famous fish geneticist, then at the Osborn Laboratories of Marine Research, at the New York Aquarium in Brooklyn, New York. Following her graduation, she joined the Center for Biomedical Research, a division of the Population Council located in New York City on the campus of the Rockefeller University. There, the main focus of her studies with Dr. Mario Ascoli was to understand the mechanisms by which hormones control the release of testosterone from testicular cells with the long-term goal of providing knowledge for the development of new contraceptive methods and clinical treatments. In 1987, she joined the laboratory of Dr. Sherwin Wilk, a pioneer in the field of protein degradation, in the Department of Pharmacology at Mount Sinai School of Medicine and in 1993 she became a research assistant professor in the same department. In 1998 she moved her laboratory to the Department of Biological Sciences at Hunter College of the City University of New York where she is an associate professor. Dr. Figueiredo-Pereira's research interest since 1987 has been to understand the mechanisms by which proteins in cells are eliminated and how the accumulation of unwanted proteins may be a major contributor to the degeneration of neurons, eventually leading to the development of disorders such as Parkinson's disease. She is particularly interested in addressing the role of the ubiquitin/proteasome pathway in neurodegeneration. This complex pathway for protein degradation eliminates proteins that have been tagged by ubiquitin. In 1994, her studies were among the first to establish that, if protein degradation is hindered by proteasome inhibitors developed by Dr. Wilk, neurons in culture acquire abnormal protein deposits that are ubiquitinated and eventually die. In 2000, her group was among the first to determine that proteasome inhibitors trigger proinflammatory responses in conjunction with the accumulation of ubiquitinated proteins in neurons. These two phenomena were also shown to be triggered by oxidative stress. The proinflammatory responses associated with proteasome inhibition may accelerate the neurodegenerative process in disorders such as Parkinson's and Alzheimer's disease, where the deposition of ubiquitinated proteins in neuronal inclusions could be linked to inflammation. Anti-inflammatory drugs as well as agents that prevent protein aggregation could be of therapeutic value to these forms of neurodegeneration. Dr. Figueiredo-Pereira's group also established a stable neuronal cell line expressing a mutant proteasome subunit that reduces proteasome activity. The effects of this genetic manipulation on neuronal homeostasis is currently being investigated in her laboratory. More recently, in an ongoing collaboration between Dr. Peter Werner's laboratory at Albert Einstein College of Medicine and Dr. Figueiredo-Pereira's laboratory at Hunter College of CUNY, a transgenic mouse model expressing the same mutant proteasome subunit is being developed. This proteasome transgenic mouse model will be used to address how proteasome dysfunction affects dopamine neuronal survival under a variety of stress conditions known to be associated with Parkinson's disease.