Dr. Nussbaum's research interests focus in three areas:

Molecular Genetics of Parkinson Disease
Parkinson disease is a slowly progressive disease of the nervous system, which strikes an estimated 50,000 mostly older Americans each year. Over the past 10 years, Dr. Nussbaum and collaborators found that mutations in the alpha-synuclein gene (SNCA) that either change a single amino acid or greatly increase its expression can cause hereditary, early onset Parkinson disease. Lewy bodies, which are protein aggregates that are a defining characteristic of all Parkinson disease, are composed primarily of alpha-synuclein, thereby providing a link between mutations in SNCA and the disease. Dr. Nussbaum's group is exploring the link between alpha-synuclein aggregates and the disease in model systems as well as studying new families with hereditary Parkinson disease to find other genes which, when altered, cause the disease.

Oculocerebrorenal Syndrome of Lowe
Lowe syndrome, formally known as Lowe oculocerebrorenal syndrome, is a rare X-chromosome-linked disorder that can cause mental retardation, seizures, cataracts, and kidney disease in young children. In 1992, Dr. Nussbaum identified a defective gene that causes Lowe syndrome. The gene, OCRL1, specifies an enzyme that appears to act primarily in protein processing and transport. The laboratory is working to determine why disabling this enzyme affects so many apparently unrelated organ systems, thereby, perhaps, pointing to possible ways that we could intervene medically in treating patients with this disorder.

Personalized Genetic Medicine
With the completion of the Human Genome Project, geneticists had a single representative sequence of the human genome. The next step was to develop a comprehensive catalog of human DNA variation for use in determining which of these variants contribute to our susceptibility to complex human diseases such as diabetes, heart disease, neurodegeneration, psychiatric illness, autoimmune disease and birth defects. Learning how to apply an individual patient's own genetic susceptibility information to clinical practice is the essence of Personalized Genetic Medicine and is a critically important step in realizing the promise of the Human Genome Project to improve health care. Dr. Nussbaum is interested in working with clinical colleagues at UCSF to study how best to apply patients' genetic information to their health care.