Carol Ann Miller
Professor, Departments of Pathology and Neurology
Co-Director of Alzheimer's Disease Research Center
Director of Neuropathology Core
Chief, Neuropathology, Los Angeles County USC Medical Center
- Neuronal specificity
- selective vulnerability neurodegeneration
- Alzheimer's disease
Research OverviewNeurospecificity is a key factor in selective vulnerability in neurodegeneration diseases. The laboratory of Dr. Carol Miller has focused on identifying and characterizing the function of genes selectively expressed or regulated in vulnerable neurons. For example, one gene, JNK3, a neuron-specific stress kinase responds to environmental stress. Defining protein-protein interactions of these signal transduction molecules has led to underlying mechanism leading to cell death caused by hypoxia/ischemia of strokes or amyloid (AB peptides) of Alzheimer's disease. We have also identified several JNK interacting proteins, including one, DENN-MADD which functions in synaptic vesicle release but under stress, leads to apoptosis.
Because of cross-interactions of many of these signal transduction pathways, Dr. Miller's group is using microarrays which define regulation of multiple genes. We are combining these methods with isolation of single, normal or diseased neurons from human post-mortem brain and linear "in cell" amplification of the mRNA. Once normal neuronal subpopulations are characterized, we can compare those from diseased brains, including affected or spared subpopulations early or late in the course of the disease. Using bioinformatics, we are defining functionally related clusters of genes. We expect this approach to identify co-regulation of known genes and lead to the discovery of new genes. Our work links observations in experimental models to mechanisms operative in the normal and diseased human brain.
- Mailing Address:
- Keck School of Medicine of USC
Department of Pathology, MCA-341A
2011 Zonal Avenue
Los Angeles, CA 90033
- Office Location:
- McKibben Annex Room 340
- Office Phone:
- (323) 442-1602
- Lab Location:
- McKibben Annex Rooms 341, 343,
- Lab Phone:
- (323) 442-1930
- (323) 442-1808
- Washington University School of Medicine, St. Louis, MO, 1966-1969.
- Pathology and Neuropathology Resident, Post-doctoral fellow; Cell Biology, Albert Einstein College of Medicine, Bronx, NY, 1969-1972.
- Assistant Professor of Neuroscience, Albert Einstein College of Medicine Bronx, NY, 1972-1977.
- M.D., Jefferson Medical College, Philadelphia, PA, 1965.
- B.A., Mount Holyoke College, So. Hadley, MA, 1961.
Gylys KH, Fein JA, Yang F, Miller CA, Cole GM. (2007) Increased cholesterol in Abeta-positive nerve terminals from Alzheimer's disease cortex. Neurobiol Aging. 28(1):8-17. -PubMed
Dong Z, Zhou L, Del Villar K, Ghanevati M, Tashjian V, Miller CA. (2005) JIP1 regulates neuronal apoptosis in response to stress. Mol Brain Res 134:282-293. -PubMed
Ghanevati M, Miller CA. (2005) Phospho-beta-catenin accumulation in Alzheimer's disease and in aggresomes due to proteasome dysfunction. J Molec Neurosci. 25(1):79-94. -PubMed
Liu Y, Dargusch R, Banh C, Miller CA, Schubert D. (2004) Detecting bioactive amyloid peptide species in Alzheimer's disease. J Neurochem 91:648-56. -PubMed
Zhou L, Del Villar K, Dong Z, Miller CA. (2004) Neurogenesis response to hypoxia-induced cell death: MAP kinase signal transduction mechanisms. Brain Res 1021:8-19. -PubMed
Del Villar K, Miller CA. (2004) Down-regulation of DENN/MADD, a TNF receptor binding protein, correlates with neuronal cell death in Alzheimer's disease brain and hippocampal neurons. PNAS 101(12):4210-15. -PubMed
Zhou L, Miller BL, McDaniel CH, Kelly L, Kim OJ, Miller CA. (1998) Fronto-temporal dementia: Neuropil spheroids and presynaptic terminal degeneration. Ann Neurol 44:88-109. -PubMed
Zhang Y, Zhou L, Miller CA. (1998) A splicing variant of a death domain protein that is regulated by a mitogen-activated kinase is a substrate for c-Jun N-terminal kinase in the human central nervous system. PNAS 95:2586-2591. -PubMed
Zhou L, Chomyn A, Attardi G, Miller CA. (1997) Myoclonic epilepsy and ragged red fibers (MERRF) Syndrome: Selective vulnerability of CNS neurons does not correlate with the level of mitochondrial tRNAlys mutation in individual neuronal isolates. J of Neurosci 17(20):7746-7753. -PubMed
Mohit A, Martin JH, Miller CA. (1995) P493F12 kinase: A novel MAP kinase expressed in a subset of neurons in the human nervous system. Neuron 14:67-78. -PubMed