Greer Murphy M.D., Ph.D.
Academic Appointments
Professional Snapshot
Professional Education
| M.D.: | University of California, Davis, (1986) |
| Ph.D.: | University of California, Berkeley, (1984) |
| B.A.: | The George Washington University, (1974) |
Scientific Focus
Current Research Interests
The first focus of our laboratory is the cerebral inflammatory reaction in Alzheimer's disease (AD). Our central hypothesis is that activation of microglial cells in AD may have certain beneficial effects on neuronal survival. We detected a large increase in expression of the receptor for macrophage colony stimulating factor (M-CSFR) on microglia in the PDAPP transgenic mouse model for AD. In cultured microglia, we found that overexpression of the M-CSFR results in microglial activation and increased phagocytosis of amyloid beta. Microglial overexpression of the M-CSF receptor also protects neurons from NMDA toxicity in a co-culture system of exogenous microglia and hippocampal organotypic cultures. Further, we have found that overexpression of the M-CSFR on microglia in organotypic cultures using biolistic gene transfer also results in protection against NMDA-induced neurotoxicity. Currently we are using oligonucleotide microarrays, proteomics, and other techniques to identify signal transduction pathways activated by the M-CSFR in microglia, and potentially neuroprotective factors produced by microglia.
The second focus of our laboratory is on genetic factors that predict response to medications (pharmacogenetics). In collaboration with clinical researchers at Stanford and elsewhere we are examining polymorphisms that affect the metabolism and/or pharmacodynamic effects of medications used in neuropsychiatry. A large bank of DNA samples from patients treated with medications having different pharmacologic actions in the brain has been assembled, along with clinical efficacy and side effect data. Polymorphisms that affect receptors, transport proteins, and metabolic enzymes are being tested as predictors of clinical outcome. We have identified several genetic markers that predict treatment discontinuations due to side effects in patients receiving widely-prescribed antidepressant medications. We are also studying the pharmacogenetics of antidepressant medications...
Clinical Trials
Publications
- FKBP5 Polymorphisms and Antidepressant Response in Geriatric Depression American Journal of Medical Genetics, Part B Neuropsychiatric Genetics. 2009
- Abeta peptide conformation determines uptake and interleukin-1alpha expression by primary microglial cells. Neurobiol Aging. 2009; (11): 1792-804
- Gene expression profile of the PDAPP mouse model for Alzheimer's disease with and without Apolipoprotein E. Neurobiol Aging. 2009; (4): 574-90
- Cerebral Inflammation and Alzheimer's Dementia In: Research Progress in Alzheimer's Disease and Dementia, vol. 2, edited by Miao-Kun Sun. 2007: 57-96
- Extended cognitive behavior therapy for cigarette smoking cessation. Addiction. 2008; (8): 1381-90
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