Grant W. Anderson, Ph.D. Assistant Professor Department of Pharmacy Practice and Pharmaceutical Sciences Office: 117 Life Science, Duluth Telephone Number: 218-726-6007 E-mail Address: ander163@umn.edu

Education:

Fellowship Training, University of Minnesota
Ph.D., Microbiology, University of Minnesota
B.S., Microbiology, Genetics and Cell Biology, University of Minnesota

Course Directorships:

Phar 6141, Medical Microbiology and Immunizations
Phar 6153, Pharmaceutical Immunology
Phar 6158, Recombinant DNA-derived Drugs

Professional Memberships:

American Association for the Advancement of Science (AAAS)
American Thyroid Association (ATA)
The Endocrine Society

Research Interests:

Thyroid hormone, brain development, nutritional regulation of gene expression, lipid metabolism.

Thyroid hormone deficiency during fetal and early childhood development is a major worldwide public health problem causing mental retardation and irreversible brain damage. The long-term goal of this research program is to understand the mechanism by which thyroid hormone (TH) regulates mammalian brain development.

Development of the mammalian brain is a complex event involving a variety of cell types all of which must proliferate, migrate and differentiate in a spatially and temporally defined pattern. Signaling molecules such as TH provide a mechanism that allows cells in disparate regions of the brain to develop in a synchronous fashion. In the rat, normal brain development is dependent on the TH signal for a brief window of time. During this period of time TH transcriptionally activates specific brain genes. However, prior to this period of brain development these genes are resistant to TH. Likewise, after development is completed, the brain becomes refractory to TH.

Further research should reveal mechanisms of TH control not previously described and may provide a mechanism for artificially controlling the expression of genes during specific stages of brain development. Manipulating the expression of these genes in the mature animal could provide important therapeutic applications for treatment of ailments such as brain and spinal cord injury or multiple sclerosis.

Studies in our laboratory attempt to determine the molecular mechanisms involved in transient regulation of these TH-responsive brain genes. We have selected developing oligodendrocytes and Purkinje cells as glial and neuronal model cells in which to study the factors that control TH action in the brain. The oligodendrocyte specific myelin basic protein gene and the Purkinje cell specific Purkinje cell protein-2 gene have been chosen as model genes for these studies. Research from our laboratory has determined that transient control of TH action is likely exerted at the promoter level in these model cells. Further research should reveal mechanisms of TH control not previously described and may provide a mechanism for artificially controlling the expression of genes during specific stages of brain development. Manipulating the expression of these genes in the mature animal could provide important therapeutic applications for treatment of ailments such as brain and spinal cord injury or multiple sclerosis.

Our research program also studies the mechanisms by which TH and dietary sugars regulate the expression of genes involved in lipid synthesis. Both an increase in TH levels and an increase in the consumption of dietary sucrose stimulate the genes that produce long chain fatty acids in the liver and in fat. Both these factors interact synergistically to regulate these genes. In the absence of TH, dietary sugars cannot effectively induce the lipogenic enzyme genes. Similarly, in fasted animals the administration of TH is associated with markedly decreased response of these genes. An understanding of the regulation of this system will allow us to develop strategies to effectively treat diseases such as obesity or prevent complications from diseases associated with metabolic dysfunction such as diabetes mellitus.

Research Techniques Used:

Primary brain cell culture
In situ hybridization and immunohistochemistry
Transfection
Chromosomal immunoprecipitation
Real time RT-PCR
Creation of "knockout" mice

Recent Publications:

Anderson GW, Hagen SG, Larson RJ, Strait KA, Schwartz HL, Oppenheimer JH. (1997) Purkinje cell protein-2 cis-elements mediate repression of T3-dependent transcriptional activation. Molecular and Cellular Endocrinology 131:79-87.

Anderson GW, Larson RJ, Oas DR, Sandhofer CR, Schwartz HL, Mariash CN, Oppenheimer JH. Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) modulates expression of the Purkinje cell protein-2 gene: A potential role for COUP-TF in repressing premature thyroid hormone action in the developing brain. (1998) The Journal of Biological Chemistry 273(26):16391-16399.

Chen Z, Li K, Rowland RRR, Anderson GW, Plagemann PGW. Lactate dehydrogenase-elevating virus variants: cosegregation of neuropathogenicity and impaired capability for high viremic persistent infection. (1998) Journal of NeuroVirology 4:560-568.

Anderson GW, Mariash CN, Oppenheimer JH. Molecular actions of thyroid hormone. In: Braverman LE, Utiger RD, eds. (2000) Werner and Ingbar's The Thyroid. Philadelphia, Lippincott Williams and Wilkins, 174-195.

Anderson GW. Thyroid hormones and the brain. (2001) Frontiers in Neuroendocrinology 22:1-17.

Zhu Q, Mariash A., Margosian MR, Gopinath S, Fareed MT, Anderson GW, Mariash CN. Spot 14 gene deletion increases hepatic de novo lipogenesis. (2001) Endocrinology 142(10):4363-70.

Anderson GW, Mariash CN. Molecular aspects of thyroid hormone-regulated behavior. In: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RT, eds. (2002) Hormones, Brain and Behavior. Academic Press, 539-566.

Jones SA, Jolson DM, Cuta KK, Mariash CN, Anderson GW. Triiodothyronine is a survival factor for developing oligodendrocytes. (2003) Molecular and Cellular Endocrinology 199(1):49-60.

Arnold AM, Anderson GW, McIver B, Eberhardt NL. A novel dynamin III isoform is negatively regulated by thyroid hormone in the central nervous system. (2003) International Journal of Developmental Neuroscience 21(5):267-75.

Anderson GW, Schoonover C, Jones SA. Control of thyroid hormone action in the developing rat brain. (2003) Thyroid 13(11): 1039-1056.

Campbell MC, Anderson GW, Mariash CN. The human and rat S14 genes are differentially regulated by thyroid hormone. (2003) Endocrinology 144(12): 5242-5248.

Schoonover CR, Seibel MM, Jolson DM, Stack MJ, Rahman R, Jones SA, Mariash CN, Anderson GW. Thyroid hormone regulates oligodendrocyte accumulation in developing rat brain white matter tracts. (2004) Endocrinology. 145(11): 5013-5020.

Jones SA, Thoemke KR, Anderson GW. The role of thyroid hormone in fetal and neonatal brain development. (2005) Current Opinion in Endocrinology and Diabetes 12:10-16.

Anderson GW, Zhu Q, Mucha GT, Parks EJ, Metkowski JK, Mariash CN. The Spot 14 protein is required for de novo lipid synthesis in the lactating mammary gland. (2005) Endocrinology 146 (8):3343-50.

Anderson GW. Thyroid hormone and cerebellar development. (2007) The Cerebellum 18:1-15.

Westholm DE, Rumbley JN, Salo DR, Rich TP, Anderson GW. Organic anion transporting polypeptides at the blood-brain and blood-cerebrospinal fluid barriers. (2007) Current Topics in Developmental Biology.

Anderson GW, Zhu Q, Metkowski JK, Stack MJ, Gopinath S, Mariash CN. The Spot 14 null mouse is resistant to diet induced obesity. In press. Metabolism Clinical and Experimental.

Westholm DE, Stenehjem DD, Rumbley JN, Anderson GW. The fenamic acid class of NSAIDS are transported by organic anion transporting polypeptide 1c1 in brain microvessels. Submitted. Endocrinology.

Bastian TW, Stack MJ, Stenehjem DD, Westholm Drewes LR, Mariash CN, Anderson GW. Thyroid hormone transporter gene expression during brain development. In preparation.