John D. Fryer, Ph.D., Post-doc

Phone: 713-798-4993
E-mail: jfryer@bcm.edu

Joined the lab: May 2005

Education:
B.S. in Microbiology from the University of Arizona;
Ph.D. in Neurosciences from Washington University in St. Louis, MO.

Project: Role of capicua in development and spinocerebellar ataxia type 1.

Spinocerebellar ataxia type 1 (SCA1) is caused by a polyglutamine expansion in the protein ataxin-1.  Several lines of evidence suggest that an enhanced normal function or gain of function of this protein leads to the disease phenotype.  Thus, determining the normal function of this protein will elucidate mechanisms of the disease. We have found that a SOX-like transcription factor Capicua (Cic) strongly associates with the ataxin-1 protein in vivo, however, very little is known about this gene.  Additionally, our data thus far show that Cic and ataxin-1 have a very similar pattern of expression in the brain.  The aim of my fellowship is to understand the normal function of Cic in vivo as well as understand its role in SCA1.

Selected publications:

1. Fryer JD, Lukas RJ.  Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine.  J Pharmacol Exp Ther. 1999, 288(1):88-92.
2. Fryer JD, Lukas RJ.  Antidepressants noncompetitively inhibit nicotinic acetylcholine receptor function.  J Neurochem. 1999, 72(3):1117-24.
3. Fagan AM, Younkin LH, Morris JC, Fryer JD, Cole TG, Younkin SG, Holtzman DM. Differences in the Abeta40/Abeta42 ratio associated with cerebrospinal fluid lipoproteins as a function of apolipoprotein E genotype.  Ann Neurol. 2000, 48(2):201-10.
4. Han BH, DeMattos R, Dugan L, Kim-Han J, Brendza R, Fryer JD, Kierson M, Cirrito J, Quick K, Harmony J, Aronow B, Holtzman DM.  Clusterin/apolipoprotein J deficient mice: Decreased brain injury via a caspase-3 independent pathway in a model of cerebral palsy.  Nat Med. 2001, 7:338-343.
5. Fryer JD, Taylor JW, DeMattos RB, Bales KR, Paul SM, Parsadanian M, Holtzman DM. Apolipoprotein E markedly facilitates age-dependent cerebral amyloid angiopathy and spontaneous hemorrhage in amyloid precursor protein transgenic mice.  J Neurosci. 2003, 23(21):7889-96.
6. Lee JM, Yin KJ, Hsin I, Chen S, Fryer JD, Holtzman DM, Hsu CY, Xu J. Matrix metalloproteinase-9 and spontaneous hemorrhage in an animal model of cerebral amyloid angiopathy.  Ann Neurol. 2003, 54(3):379-82.
7. Wahrle SE, Jiang H, Parsadanian M, Legleiter J, Han X, Fryer JD, Kowalewski T, Holtzman DM. ABCA1 is required for normal CNS apoE levels and for lipidation of astrocyte-secreted apoE.  J Biol Chem. 2004, 279(39):40987-93.
8. Fryer JD, Simmons K, Parsadanian M, Bales KR, Paul SM, Sullivan PM, Holtzman DM. Human apoE4 alters the amyloid-beta 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an APP transgenic model.  J Neurosci. 2005, 25(11):2803-10.
9. Fryer JD, DeMattos RB, McCormick LM, O’Dell MA, Spinner ML, Bales KR, Paul SM, Parsadanian M, Bu G, Holtzman DM. The Low Density Lipoprotein Receptor Regulates the Level of Central Nervous System Human and Murine Apolipoprotein E but Does Not Modify Amyloid Plaque Pathology in PDAPP Mice. J Biol Chem. 2005, 280(27):25754-25759.
10. Fryer JD, Holtzman DM. The Bad Seed in Alzheimer’s Disease. Neuron. 47(2):167-8.